A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function Academic Article uri icon

Overview

MeSH Major

  • Cell Survival
  • Diabetes Mellitus, Type 2
  • Hypoglycemic Agents
  • Insulin-Secreting Cells
  • Peptide Fragments

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.

publication date

  • July 3, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3695697

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2012.05.011

PubMed ID

  • 22768837

Additional Document Info

start page

  • 33

end page

  • 43

volume

  • 16

number

  • 1