Islet neogenesis associated protein increases the expression of several proteins involved in growth and differentiation of neonatal rat pancreatic islets

BARBOSA H; SILVA K; BORDIN S; CARNEIRO E; BORELLI M; GAGLIARDINO J; BOSCHERO AC

Helsingor, Dinamarca

Simposio; EASD Islet Study Group Symposium 2006. Beta cell replacement/regeneration in diabetes therapy; 2006

European Association for the Study of Diabetes

The Islet Neogenesis Associated Protein (INGAP), a polypeptide originally isolated from cellophane wrapped pancreas of hamsters, increases pancreatic B-cell mass and potentiates glucose-induced insulin secretion. In this study, we further investigated the effects of a pentadecapeptide having the 104-118 amino acid sequence of INGAP (INGAP-PP) on the mechanism of insulin secretion in neonatal pancreatic rat islets, maintained in culture for 4 days. INGAP-PP treatment increased the gene and protein expression of SUR1, Kir6.2 and M3 muscarinic receptor sub-type. INGAP-PP also increased AKT1, mTOR, PHAS-I, ERK2, and MEKK1 gene expression as well as ERK1/2 protein phosphorylation compared with control islets. The insulin secretion, induced by glucose (8.3 and 16.7 mM), tobutamide (100 µM) and carbachol (200 µM) was also significantly higher in INGAP-PP treated islets. These results suggest that INGAP modulates growth and differentiation of pancreatic B-cells by up-regulating proteins involved in P13K and MAPK pathways. The increase of insulin secretion induced by glucose, carbachol and tolbutamide, associated with the increased expression of M3 muscarinic receptor sub-type as well as proteins that form the KATP-channels, also indicate that INGAP directly affects important steps of the insulin secretion mechanism.