| Literature DB >> 22768837 |
Samuel B Stephens1, Jonathan C Schisler, Hans E Hohmeier, Jie An, Albert Y Sun, Geoffrey S Pitt, Christopher B Newgard.
Abstract
Deterioration of functional islet β-cell mass is the final step in progression to Type 2 diabetes. We previously reported that overexpression of Nkx6.1 in rat islets has the dual effects of enhancing glucose-stimulated insulin secretion (GSIS) and increasing β-cell replication. Here we show that Nkx6.1 strongly upregulates the prohormone VGF in rat islets and that VGF is both necessary and sufficient for Nkx6.1-mediated enhancement of GSIS. Moreover, the VGF-derived peptide TLQP-21 potentiates GSIS in rat and human islets and improves glucose tolerance in vivo. Chronic injection of TLQP-21 in prediabetic ZDF rats preserves islet mass and slows diabetes onset. TLQP-21 prevents islet cell apoptosis by a pathway similar to that used by GLP-1, but independent of the GLP-1, GIP, or VIP receptors. Unlike GLP-1, TLQP-21 does not inhibit gastric emptying or increase heart rate. We conclude that TLQP-21 is a targeted agent for enhancing islet β-cell survival and function.Entities:
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Year: 2012 PMID： 22768837 PMCID： PMC3695697 DOI： 10.1016/j.cmet.2012.05.011
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287