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Stimulating β-cell regeneration by combining a GPR119 agonist with a DPP-IV inhibitor

Ansarullah1, Yan Lu, Martha Holstein

  • 1The Sanford Project, Children Health Research Center, Sanford Research/USD, Sioux Falls, South Dakota, United States of America.

Plos One
|February 6, 2013
PubMed
Abstract

Insights

Combining a GPR119 agonist with a DPP-IV inhibitor shows promise for diabetes treatment. This combination therapy effectively promotes beta-cell regeneration and reverses diabetes in mice.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Regenerative Medicine

Background:

  • G-protein coupled receptor 119 (GPR119) agonists stimulate glucagon-like peptide-1 (GLP-1) release.
  • GLP-1 is rapidly degraded by dipeptidylpeptidase-IV (DPP-IV).
  • Investigating combination therapy for enhanced therapeutic outcomes in diabetes.

Purpose of the Study:

  • To evaluate the efficacy of combining a GPR119 agonist (PSN632408) with a DPP-IV inhibitor (sitagliptin).
  • To assess the impact on beta-cell regeneration and diabetes reversal in a mouse model.

Main Methods:

  • Diabetes was induced in C57BL/6 mice using streptozotocin.
  • Mice received PSN632408, sitagliptin, or combination therapy for 7 weeks.
  • Evaluated blood glucose, oral glucose tolerance, active GLP-1, beta-cell mass, cell replication, and neogenesis.

Main Results:

  • Combination therapy led to normoglycemia in 59% of treated mice.
  • Significantly increased plasma active GLP-1 levels and improved glucose clearance.
  • Stimulated alpha- and beta-cell replication, augmented beta-cell mass, and induced beta-cell neogenesis.

Conclusions:

  • Combining a GPR119 agonist with a DPP-IV inhibitor is a potential novel therapeutic strategy.
  • This approach shows promise for stimulating beta-cell regeneration.
  • The combination therapy may offer a new avenue for reversing diabetes.

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