Journal article
A VGF-Derived Peptide Attenuates Development of Type 2 Diabetes via Enhancement of Islet β-Cell Survival and Function
Cell metabolism, Vol.16(1), pp.33-43
07/03/2012
DOI: 10.1016/j.cmet.2012.05.011
PMCID: PMC3695697
PMID: 22768837
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.
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► Nkx6.1 overexpression in rat islets strongly upregulates the prohormone VGF ► VGF peptide TLQP-21 potentiates glucose-stimulated insulin secretion ► TLQP-21 treatment of ZDF rats improves glycemic control and preserves islet mass ► Antiapoptotic action of TLQP-21 occurs via a PKA, IGF1R, PI3K-dependent pathway
Details
- Title: Subtitle
- A VGF-Derived Peptide Attenuates Development of Type 2 Diabetes via Enhancement of Islet β-Cell Survival and Function
- Creators
- Samuel B Stephens - Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704, USAJonathan C Schisler - Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704, USAHans E Hohmeier - Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704, USAJie An - Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704, USAAlbert Y Sun - Division of Cardiovascular Diseases, Duke University Medical Center, Durham, NC 27704, USAGeoffrey S Pitt - Department of Pharmacology and Cancer Biology and Department of Medicine, Duke University Medical Center, Durham, NC 27704, USAChristopher B Newgard - Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27704, USA
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.16(1), pp.33-43
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2012.05.011
- PMID
- 22768837
- PMCID
- PMC3695697
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English
- Date published
- 07/03/2012
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094519302771
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