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Citations to this article

Islet β cell expression of constitutively active Akt1/PKBα induces striking hypertrophy, hyperplasia, and hyperinsulinemia
Ernesto Bernal-Mizrachi, … , Cris M. Welling, M. Alan Permutt
Ernesto Bernal-Mizrachi, … , Cris M. Welling, M. Alan Permutt
Published December 1, 2001
Citation Information: J Clin Invest. 2001;108(11):1631-1638. https://doi.org/10.1172/JCI13785.
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Article

Islet β cell expression of constitutively active Akt1/PKBα induces striking hypertrophy, hyperplasia, and hyperinsulinemia

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Abstract

The phosphoinositide 3-kinase–Akt/PKB pathway mediates the mitogenic effects various nutrients and growth factors in cultured cells. To study its effects in vivo in pancreatic islet β cells, we created transgenic mice that expressed a constitutively active Akt1/PKBα linked to an Insulin gene promoter. Transgenic mice exhibited a grossly visible increase in islet mass, largely due to proliferation of insulin-containing β cells. Morphometric analysis verified a six-fold increase in β cell mass/pancreas, a two-fold increase in 5-bromo-2′-deoxyuridine incorporation, a four-fold increase in the number of β cells per pancreas area, and a two-fold increase in cell size in transgenic compared with wild-type mice at 5 weeks. At least part of the increase in β cell number may be accounted for by neogenesis, defined by criteria that include β cells proliferating from ductular epithelium, and by a six-fold increase in the number of single and doublet β cells scattered throughout the exocrine pancreas of the transgenic mice. Glucose tolerance was improved, and fasting as well as fed insulin was greater compared with wild-type mice. Glucose-stimulated insulin secretion was maintained in transgenic mice, which were resistant to streptozotocin–induced diabetes. We conclude that activation of the Akt1/PKBα pathway affects islet β cell mass by alteration of size and number.

Authors

Ernesto Bernal-Mizrachi, Wu Wen, Sarah Stahlhut, Cris M. Welling, M. Alan Permutt

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 Total
Citations: 1 6 13 5 10 8 5 7 8 9 7 14 10 12 9 20 14 19 8 5 6 4 4 2 1 207
Citation information
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Citations to this article in year 2008 (19)

Title and authors Publication Year
FoxO1 Mediates Insulin-Dependent Regulation of Hepatic VLDL Production
Adama Kamagate1, Shen Qu1, German Perdomo1, Dongming Su1, Dae Hyun Kim1, Sandra Slusher1, Marcia Meseck2 and H. Henry Dong1
Journal of Clinical Investigation 2008
S6 Kinase 1 is required for Akt1-mediated Insulinoma, but not pancreatic b cell Hypertrophy
Samira Alliouachene , Robyn L. Tuttle , Stephanie Boumard , Thomas Lapointe , Sophie Berissi , Stephane Germain , Francis Jaubert , David Tosh , Morris J. Birnbaum , Mario Pende
Journal of Clinical Investigation 2008
Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice
Y Shigeyama, T Kobayashi, Y Kido, N Hashimoto, SI Asahara, T Matsuda, A Takeda, T Inoue, Y Shibutani, M Koyanagi, T Uchida, M Inoue, O Hino, M Kasuga, T Noda
Molecular and cellular biology 2008
Regulation of pancreas plasticity and malignant transformation by Akt signaling
L Elghazi, AJ Weiss, DJ Barker, J Callaghan, L Staloch, EP Sandgren, M Gannon, VN Adsay, E Bernal-Mizrachi
Gastroenterology 2008
Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age
MV Chakravarthy, Y Zhu, MB Wice, T Coleman, KL Pappan, CA Marshall, ML McDaniel, CF Semenkovich
Diabetes 2008
Glial Cell Line-Derived Neurotrophic Factor increases beta cell mass and improves glucose tolerance
S Mwangi, M Anitha, C Mallikarjun, X Ding, M Hara, A Parsadanian, CP Larsen, P Thule, SV Sitaraman, F Anania, S Srinivasan
Gastroenterology 2008
Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance
K Tanabe, Z Liu, S Patel, BW Doble, L Li, C Cras-Méneur, SC Martinez, CM Welling, MF White, E Bernal-Mizrachi, JR Woodgett, MA Permutt
PLoS Biology 2008
IGF-I mediates regeneration of endocrine pancreas by increasing beta cell replication through cell cycle protein modulation in mice
J Agudo, E Ayuso, V Jimenez, A Salavert, A Casellas, S Tafuro, V Haurigot, J Ruberte, JC Segovia, J Bueren, F Bosch
Diabetologia 2008
β-cell failure as a complication of diabetes
KJ Chang-Chen, R Mullur, E Bernal-Mizrachi
Reviews in Endocrine and Metabolic Disorders 2008
Genetic modelling of the PTEN/AKT pathway in cancer research
O Renner, C Blanco-Aparicio, A Carnero
Clinical and Translational Oncology 2008
Mice with beta cell overexpression of glycogen synthase kinase-3β have reduced beta cell mass and proliferation
Z Liu, K Tanabe, E Bernal-Mizrachi, MA Permutt
Diabetologia 2008
Experimental models of hepatocellular carcinoma
P Newell, A Villanueva, SL Friedman, K Koike, JM Llovet
Journal of Hepatology 2008
Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner
L Rachdi, N Balcazar, F Osorio-Duque, L Elghazi, A Weiss, A Gould, KJ Chang-Chen, MJ Gambello, E Bernal-Mizrachi
Proceedings of the National Academy of Sciences 2008
Exendin-4 Stimulation of Cyclin A2 in  -Cell Proliferation
WJ Song, WE Schreiber, E Zhong, FF Liu, BD Kornfeld, FE Wondisford, MA Hussain
Diabetes 2008
Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice
XD Wang, MZ Vatamaniuk, SK Wang, CA Roneker, RA Simmons, XG Lei
Diabetologia 2008
Constitutively Active Akt Induces Enhanced Myelination in the CNS
AI Flores, SP Narayanan, EN Morse, HE Shick, X Yin, G Kidd, RL Avila, DA Kirschner, WB Macklin
The Journal of neuroscience : the official journal of the Society for Neuroscience 2008
Trefoil Factor 3 Stimulates Human and Rodent Pancreatic Islet β-Cell Replication with Retention of Function
PT Fueger, JC Schisler, D Lu, DA Babu, RG Mirmira, CB Newgard, HE Hohmeier
Molecular Endocrinology 2008
Insulin Stimulates Primary β-Cell Proliferation via Raf-1 Kinase
JL Beith, EU Alejandro, JD Johnson
Endocrinology 2008
Stimulation of Human and Rat Islet β-Cell Proliferation with Retention of Function by the Homeodomain Transcription Factor Nkx6.1
JC Schisler, PT Fueger, DA Babu, HE Hohmeier, JS Tessem, D Lu, TC Becker, B Naziruddin, M Levy, RG Mirmira, CB Newgard
Molecular and cellular biology 2008

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