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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 2013 (10)

Title and authors Publication Year
PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16(ink4a.)
N Zeng, KT Yang, JA Bayan, L He, R Aggarwal, JW Stiles, X Hou, V Medina, D Abad, BM Palian, I Al-Abdullah, F Kandeel, DL Johnson, BL Stiles
Aging Cell 2013
Adult-onset deletion of Pten increases islet mass and beta cell proliferation in mice
KT Yang, JA Bayan, N Zeng, R Aggarwal, L He, Z Peng, A Kassa, M Kim, Z Luo, Z Shi, V Medina, K Boddupally, BL Stiles
Diabetologia 2013
Update on the protective molecular pathways improving pancreatic beta-cell dysfunction
A Puddu, R Sanguineti, F Mach, F Dallegri, GL Viviani, F Montecucco
Mediators of Inflammation 2013
Quercetin Preserves β-Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation
JM Li, W Wang, CY Fan, MX Wang, X Zhang, QH Hu, LD Kong
Evidence-Based Complementary and Alternative Medicine 2013
Distinct and opposing roles for the phosphatidylinositol 3-OH kinase catalytic subunits p110α and p110β in the regulation of insulin secretion from rodent and human beta cells
J Kolic, AF Spigelman, G Plummer, E Leung, C Hajmrle, T Kin, AM Shapiro, JE Fox, PE MacDonald
Diabetologia 2013
CCCTC-binding factor mediates effects of glucose on beta cell survival
S Tsui, W Dai, L Lu
Cell Proliferation 2013
Retinal pigment epithelial cells express a functional receptor for glucagon-like peptide-1 (GLP-1)
A Puddu, R Sanguineti, F Montecucco, GL Viviani
Mediators of Inflammation 2013
Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure
J Liu, P Yu, W Qian, Y Li, J Zhao, F Huan, J Wang, H Xiao
PloS one 2013
Evidence for Rapamycin Toxicity in Pancreatic  -Cells and a Review of the Underlying Molecular Mechanisms
AD Barlow, ML Nicholson, TP Herbert
Diabetes 2013
SH2B1 in  -Cells Regulates Glucose Metabolism by Promoting  -Cell Survival and Islet Expansion
Z Chen, DL Morris, L Jiang, Y Liu, L Rui
Diabetes 2013

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