Islet neogenesis-associated protein pentadecapeptide (INGAP-PP): Mechanisms involved in its effect upon B-cell mass and function

MADRID V; DEL ZOTTO H; MAIZTEGUI B; RASCHIA MA; ALZUGARAY ME; BOSCHERO AC; BARBOSA HC; FLORES LE; BORELLI MI; GAGLIARDINO JJ

REGULATORY PEPTIDES

ELSEVIER SCIENCE BV

Año: 2009 vol. 157 p. 25 - 31

0167-0115

The effect of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) administration to normal male hamsters upon serum glucose and triglyceride levels, B-cell mass and function was studied. INGAP-PP (500 ìg) 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-B and their islets released more insulin in response to glucose; they had lower islet DNA content, significantly increased number of islets/unit area, B-cell replication rate and mass, cells co-expressing Pdx-1/ INGAP and islets in contact with ducts, and decreased B-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 B-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  eedback loop with endogenous INGAPproducing cells. Accordingly, INGAP-PP could be used to induce these effects in people with or at risk of developing diabetes.