A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Stephens, SB; Schisler, JC; Hohmeier, HE; An, J; Sun, AY; Pitt, GS; Newgard, CB

Published Date

  • July 2012

Published In

Volume / Issue

  • 16 / 1

Start / End Page

  • 33 - 43

PubMed ID

  • 22768837

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2012.05.011

Language

  • eng