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Differential and complementary effects of glucose and prolactin on islet DNA synthesis and gene expression.

Authors: Arumugam, R  Fleenor, D  Lu, D  Freemark, M 
Citation: Arumugam R, etal., Endocrinology. 2011 Mar;152(3):856-68. doi: 10.1210/en.2010-1258. Epub 2011 Jan 14.
Pubmed: (View Article at PubMed) PMID:21239441
DOI: Full-text: DOI:10.1210/en.2010-1258

The mechanisms by which lactogenic hormones promote beta-cell expansion remain poorly understood. Because prolactin (PRL) up-regulates beta-cell glucose transporter 2, glucokinase, and pyruvate dehydrogenase activities, we reasoned that glucose availability might mediate or modulate the effects of PRL on beta-cell mass. Here, we used male rat islets to show that PRL and glucose have differential but complementary effects on the expression of cell cyclins, cell cycle inhibitors, and various other genes known to regulate beta-cell replication, including insulin receptor substrate 2, IGF-II, menin, forkhead box protein M1, tryptophan hydroxylase 1, and the PRL receptor. Differential effects on gene expression are associated with synergistic effects of glucose and PRL on islet DNA synthesis. The effects of PRL on gene expression are mirrored by beta-cell overexpression of signal transducer and activator of transcription 5b and are opposed by dexamethasone. An ad-small interfering RNA specific for cyclin D2 attenuates markedly the effects of PRL on islet DNA synthesis. Our studies suggest a new paradigm for the control of beta-cell mass and insulin production by hormones and nutrients. PRL up-regulates beta-cell glucose uptake and utilization, whereas glucose increases islet PRL receptor expression and potentiates the effects of PRL on cell cycle gene expression and DNA synthesis. These findings suggest novel targets for prevention of neonatal glucose intolerance and gestational diabetes and may provide new insight into the pathogenesis of beta-cell hyperplasia in obese subjects with insulin resistance.

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CRRD Object Information
CRRD ID: 9589145
Created: 2014-11-10
Species: All species
Last Modified: 2014-11-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.