A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function.
Cell Metab, 2012/7/03;16(1):33-43.
Stephens SB[1], Schisler JC, Hohmeier HE, An J, Sun AY, Pitt GS, Newgard CB
Affiliations
PMID: 22768837DOI: 10.1016/j.cmet.2012.05.011
Impact factor: 31.373
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.
MeSH terms
Animals; Apoptosis; Area Under Curve; Blood Glucose; Cell Survival; Cells, Cultured; Cyclic AMP; Diabetes Mellitus, Type 2; Gastric Emptying; Gene Expression; Glucose; Heart Rate; Homeodomain Proteins; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Neuropeptides; Peptide Fragments; Rats; Rats, Wistar; Trans-Activators
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