Islet neogenesis-associated protein (INGAP): The role of its endogenous production as a positive modulator of insulin secretion

FLORES L; DEL ZOTTO H; FRAGAPANE F; MAIZTEGUI B; ROMAN CL; BOSCHERO CA

REGULATORY PEPTIDES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 192 p. 30 - 34

0167-0115

ABSTRACT Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene, enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a ?physiological? positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.