Journal
REGULATORY PEPTIDES
Volume 157, Issue 1-3, Pages 25-31Publisher
ELSEVIER
DOI: 10.1016/j.regpep.2009.05.011
Keywords
beta-cell apoptosis; beta-cell mass; beta-cell neogenesis; Homa-IR; Insulin secretion in vitro and in vivo
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Funding
- FONCYT
- CONICET
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The effect of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) administration to normal male hamsters upon serum glucose and triglyceride levels, beta-cell mass and function was studied. INGAP-PP (500 mu g) or saline was injected twice daily during 10 days. Both groups showed comparable body weight, serum glucose and triglyceride levels. INGAP-PP treated animals had significantly higher HOMA-IR and HOMA-beta and their islets released more insulin in response to glucose; they had lower islet DNA content, significantly increased number of islets/unit area, beta-cell replication rate and mass, cells co-expressing Pdx-1/INGAP and islets in contact with ducts, and decreased beta-cell apoptosis rate. The percentage of cells expressing Pdx-1 alone or together with INGAP or insulin increased significantly in ducts. These animals also showed a significantly higher concentration of Pdx-1 and Ngn-3 mRNA and a lower number of INGAP-positive cells. In conclusion, INGAP-PP promoted a controlled and functionally active increase of beta-cell mass; our data demonstrate for the first time the mechanism responsible for such changes; that Ngn-3 would be involved in INGAP-PP-induced neogenesis; and the existence of a negative feedback loop with endogenous INGAP-producing cells. Accordingly, INGAP-PP could be used to induce these effects in people with or at risk of developing diabetes. (c) 2009 Elsevier B.V. All rights reserved.
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