Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip
Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producin...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Blandino-Rosano, M. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2012 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag 2012 |
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| Übergeordnetes Werk: |
Enthalten in: Diabetologia - Berlin : Springer, 1965, 55(2012), 5 vom: 12. Feb., Seite 1380-1389 |
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| Übergeordnetes Werk: |
volume:55 ; year:2012 ; number:5 ; day:12 ; month:02 ; pages:1380-1389 |
| Links: |
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| DOI / URN: |
10.1007/s00125-012-2465-9 |
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| Katalog-ID: |
SPR000991341 |
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| 024 | 7 | |a 10.1007/s00125-012-2465-9 |2 doi | |
| 035 | |a (DE-627)SPR000991341 | ||
| 035 | |a (SPR)s00125-012-2465-9-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Blandino-Rosano, M. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip |
| 264 | 1 | |c 2012 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © Springer-Verlag 2012 | ||
| 520 | |a Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. | ||
| 650 | 4 | |a Akt |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Apoptosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Beta cell signalling |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Beta cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Cell cycle |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Glucose homeostasis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Insulin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Islets |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a p21 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Proliferation |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Alejandro, E. U. |4 aut | |
| 700 | 1 | |a Sathyamurthy, A. |4 aut | |
| 700 | 1 | |a Scheys, J. O. |4 aut | |
| 700 | 1 | |a Gregg, B. |4 aut | |
| 700 | 1 | |a Chen, A. Y. |4 aut | |
| 700 | 1 | |a Rachdi, L. |4 aut | |
| 700 | 1 | |a Weiss, A. |4 aut | |
| 700 | 1 | |a Barker, D. J. |4 aut | |
| 700 | 1 | |a Gould, A. P. |4 aut | |
| 700 | 1 | |a Elghazi, L. |4 aut | |
| 700 | 1 | |a Bernal-Mizrachi, E. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Diabetologia |d Berlin : Springer, 1965 |g 55(2012), 5 vom: 12. Feb., Seite 1380-1389 |w (DE-627)253722209 |w (DE-600)1458993-X |x 1432-0428 |7 nnns |
| 773 | 1 | 8 | |g volume:55 |g year:2012 |g number:5 |g day:12 |g month:02 |g pages:1380-1389 |
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10.1007/s00125-012-2465-9 doi (DE-627)SPR000991341 (SPR)s00125-012-2465-9-e DE-627 ger DE-627 rakwb eng Blandino-Rosano, M. verfasserin aut Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2012 Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. Akt (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Beta cell signalling (dpeaa)DE-He213 Beta cells (dpeaa)DE-He213 Cell cycle (dpeaa)DE-He213 Glucose homeostasis (dpeaa)DE-He213 Insulin (dpeaa)DE-He213 Islets (dpeaa)DE-He213 p21 (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Alejandro, E. U. aut Sathyamurthy, A. aut Scheys, J. O. aut Gregg, B. aut Chen, A. Y. aut Rachdi, L. aut Weiss, A. aut Barker, D. J. aut Gould, A. P. aut Elghazi, L. aut Bernal-Mizrachi, E. aut Enthalten in Diabetologia Berlin : Springer, 1965 55(2012), 5 vom: 12. Feb., Seite 1380-1389 (DE-627)253722209 (DE-600)1458993-X 1432-0428 nnns volume:55 year:2012 number:5 day:12 month:02 pages:1380-1389 https://dx.doi.org/10.1007/s00125-012-2465-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 55 2012 5 12 02 1380-1389 |
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10.1007/s00125-012-2465-9 doi (DE-627)SPR000991341 (SPR)s00125-012-2465-9-e DE-627 ger DE-627 rakwb eng Blandino-Rosano, M. verfasserin aut Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2012 Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. Akt (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Beta cell signalling (dpeaa)DE-He213 Beta cells (dpeaa)DE-He213 Cell cycle (dpeaa)DE-He213 Glucose homeostasis (dpeaa)DE-He213 Insulin (dpeaa)DE-He213 Islets (dpeaa)DE-He213 p21 (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Alejandro, E. U. aut Sathyamurthy, A. aut Scheys, J. O. aut Gregg, B. aut Chen, A. Y. aut Rachdi, L. aut Weiss, A. aut Barker, D. J. aut Gould, A. P. aut Elghazi, L. aut Bernal-Mizrachi, E. aut Enthalten in Diabetologia Berlin : Springer, 1965 55(2012), 5 vom: 12. Feb., Seite 1380-1389 (DE-627)253722209 (DE-600)1458993-X 1432-0428 nnns volume:55 year:2012 number:5 day:12 month:02 pages:1380-1389 https://dx.doi.org/10.1007/s00125-012-2465-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 55 2012 5 12 02 1380-1389 |
| allfields_unstemmed |
10.1007/s00125-012-2465-9 doi (DE-627)SPR000991341 (SPR)s00125-012-2465-9-e DE-627 ger DE-627 rakwb eng Blandino-Rosano, M. verfasserin aut Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2012 Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. Akt (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Beta cell signalling (dpeaa)DE-He213 Beta cells (dpeaa)DE-He213 Cell cycle (dpeaa)DE-He213 Glucose homeostasis (dpeaa)DE-He213 Insulin (dpeaa)DE-He213 Islets (dpeaa)DE-He213 p21 (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Alejandro, E. U. aut Sathyamurthy, A. aut Scheys, J. O. aut Gregg, B. aut Chen, A. Y. aut Rachdi, L. aut Weiss, A. aut Barker, D. J. aut Gould, A. P. aut Elghazi, L. aut Bernal-Mizrachi, E. aut Enthalten in Diabetologia Berlin : Springer, 1965 55(2012), 5 vom: 12. Feb., Seite 1380-1389 (DE-627)253722209 (DE-600)1458993-X 1432-0428 nnns volume:55 year:2012 number:5 day:12 month:02 pages:1380-1389 https://dx.doi.org/10.1007/s00125-012-2465-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 55 2012 5 12 02 1380-1389 |
| allfieldsGer |
10.1007/s00125-012-2465-9 doi (DE-627)SPR000991341 (SPR)s00125-012-2465-9-e DE-627 ger DE-627 rakwb eng Blandino-Rosano, M. verfasserin aut Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2012 Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. Akt (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Beta cell signalling (dpeaa)DE-He213 Beta cells (dpeaa)DE-He213 Cell cycle (dpeaa)DE-He213 Glucose homeostasis (dpeaa)DE-He213 Insulin (dpeaa)DE-He213 Islets (dpeaa)DE-He213 p21 (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Alejandro, E. U. aut Sathyamurthy, A. aut Scheys, J. O. aut Gregg, B. aut Chen, A. Y. aut Rachdi, L. aut Weiss, A. aut Barker, D. J. aut Gould, A. P. aut Elghazi, L. aut Bernal-Mizrachi, E. aut Enthalten in Diabetologia Berlin : Springer, 1965 55(2012), 5 vom: 12. Feb., Seite 1380-1389 (DE-627)253722209 (DE-600)1458993-X 1432-0428 nnns volume:55 year:2012 number:5 day:12 month:02 pages:1380-1389 https://dx.doi.org/10.1007/s00125-012-2465-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 55 2012 5 12 02 1380-1389 |
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10.1007/s00125-012-2465-9 doi (DE-627)SPR000991341 (SPR)s00125-012-2465-9-e DE-627 ger DE-627 rakwb eng Blandino-Rosano, M. verfasserin aut Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2012 Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. Akt (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Beta cell signalling (dpeaa)DE-He213 Beta cells (dpeaa)DE-He213 Cell cycle (dpeaa)DE-He213 Glucose homeostasis (dpeaa)DE-He213 Insulin (dpeaa)DE-He213 Islets (dpeaa)DE-He213 p21 (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 Alejandro, E. U. aut Sathyamurthy, A. aut Scheys, J. O. aut Gregg, B. aut Chen, A. Y. aut Rachdi, L. aut Weiss, A. aut Barker, D. J. aut Gould, A. P. aut Elghazi, L. aut Bernal-Mizrachi, E. aut Enthalten in Diabetologia Berlin : Springer, 1965 55(2012), 5 vom: 12. Feb., Seite 1380-1389 (DE-627)253722209 (DE-600)1458993-X 1432-0428 nnns volume:55 year:2012 number:5 day:12 month:02 pages:1380-1389 https://dx.doi.org/10.1007/s00125-012-2465-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 55 2012 5 12 02 1380-1389 |
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Blandino-Rosano, M. @@aut@@ Alejandro, E. U. @@aut@@ Sathyamurthy, A. @@aut@@ Scheys, J. O. @@aut@@ Gregg, B. @@aut@@ Chen, A. Y. @@aut@@ Rachdi, L. @@aut@@ Weiss, A. @@aut@@ Barker, D. J. @@aut@@ Gould, A. P. @@aut@@ Elghazi, L. @@aut@@ Bernal-Mizrachi, E. @@aut@@ |
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| author |
Blandino-Rosano, M. |
| spellingShingle |
Blandino-Rosano, M. misc Akt misc Apoptosis misc Beta cell signalling misc Beta cells misc Cell cycle misc Glucose homeostasis misc Insulin misc Islets misc p21 misc Proliferation Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip |
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Blandino-Rosano, M. |
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1432-0428 |
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Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip Akt (dpeaa)DE-He213 Apoptosis (dpeaa)DE-He213 Beta cell signalling (dpeaa)DE-He213 Beta cells (dpeaa)DE-He213 Cell cycle (dpeaa)DE-He213 Glucose homeostasis (dpeaa)DE-He213 Insulin (dpeaa)DE-He213 Islets (dpeaa)DE-He213 p21 (dpeaa)DE-He213 Proliferation (dpeaa)DE-He213 |
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misc Akt misc Apoptosis misc Beta cell signalling misc Beta cells misc Cell cycle misc Glucose homeostasis misc Insulin misc Islets misc p21 misc Proliferation |
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misc Akt misc Apoptosis misc Beta cell signalling misc Beta cells misc Cell cycle misc Glucose homeostasis misc Insulin misc Islets misc p21 misc Proliferation |
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misc Akt misc Apoptosis misc Beta cell signalling misc Beta cells misc Cell cycle misc Glucose homeostasis misc Insulin misc Islets misc p21 misc Proliferation |
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Diabetologia |
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| title |
Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip |
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(DE-627)SPR000991341 (SPR)s00125-012-2465-9-e |
| title_full |
Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip |
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Blandino-Rosano, M. |
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Diabetologia |
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2012 |
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Blandino-Rosano, M. Alejandro, E. U. Sathyamurthy, A. Scheys, J. O. Gregg, B. Chen, A. Y. Rachdi, L. Weiss, A. Barker, D. J. Gould, A. P. Elghazi, L. Bernal-Mizrachi, E. |
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Elektronische Aufsätze |
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Blandino-Rosano, M. |
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10.1007/s00125-012-2465-9 |
| title_sort |
enhanced beta cell proliferation in mice overexpressing a constitutively active form of akt and one allele of p21cip |
| title_auth |
Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip |
| abstract |
Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. © Springer-Verlag 2012 |
| abstractGer |
Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. © Springer-Verlag 2012 |
| abstract_unstemmed |
Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. These studies imply that $ p21^{Cip} $ could play important roles in the adaptive responses of beta cells to proliferate in conditions such as in insulin resistance. © Springer-Verlag 2012 |
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Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip |
| url |
https://dx.doi.org/10.1007/s00125-012-2465-9 |
| remote_bool |
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| author2 |
Alejandro, E. U. Sathyamurthy, A. Scheys, J. O. Gregg, B. Chen, A. Y. Rachdi, L. Weiss, A. Barker, D. J. Gould, A. P. Elghazi, L. Bernal-Mizrachi, E. |
| author2Str |
Alejandro, E. U. Sathyamurthy, A. Scheys, J. O. Gregg, B. Chen, A. Y. Rachdi, L. Weiss, A. Barker, D. J. Gould, A. P. Elghazi, L. Bernal-Mizrachi, E. |
| ppnlink |
253722209 |
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c |
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| doi_str |
10.1007/s00125-012-2465-9 |
| up_date |
2024-07-03T19:32:46.594Z |
| _version_ |
1803587594856955904 |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR000991341</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519192625.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201001s2012 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00125-012-2465-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR000991341</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00125-012-2465-9-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Blandino-Rosano, M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Enhanced beta cell proliferation in mice overexpressing a constitutively active form of Akt and one allele of p21Cip</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2012</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Springer-Verlag 2012</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Aims/hypothesis The ability of pancreatic beta cells to proliferate is critical both for normal tissue maintenance and in conditions where there is an increased demand for insulin. Protein kinase B (Akt) plays a major role in promoting proliferation in many cell types, including the insulin-producing beta cells. We have previously reported that mice overexpressing a constitutively active form of Akt (caAktTg) show enhanced beta cell proliferation that is associated with increased protein levels of cyclin D1, cyclin D2 and cyclin-dependent kinase inhibitor 1A ($ p21^{Cip} $). In the present study, we sought to assess the mechanisms responsible for augmented $ p21^{Cip} $ levels in caAktTg mice and test the role of $ p21^{Cip} $ in the proliferative responses induced by activation of Akt signalling. Methods To gain a greater understanding of the relationship between Akt and $ p21^{Cip} $, we evaluated the mechanisms involved in the modulation of $ p21^{Cip} $ by Akt and the in vivo role of reduced $ p21^{Cip} $ in proliferative responses induced by Akt. Results Our experiments showed that Akt signalling regulates p21Cip transcription and protein stability. caAktTg/p21Cip+/− mice exhibited fasting and fed hypoglycaemia as well as hyperinsulinaemia when compared with caAktTg mice. Glucose tolerance tests revealed improved glucose tolerance in caAktTg/p21Cip+/− mice compared with caAktTg. These changes resulted from increased proliferation, survival and beta cell mass in caAktTg/p21Cip+/− compared with caAktTg mice. Conclusions/interpretation Our data indicate that increased $ p21^{Cip} $ levels in caAktTg mice act as a compensatory brake, protecting beta cells from unrestrained proliferation. 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