Transcription, Expression and Binding in vivo of Islet Neogenesis-Associated Protein (INGAP) and INGAP-Analogous in Hamsters

BORELLI MI; FLORES LE; GARCÍA ME; BOSCHERO AC; DEL ZOTTO H; GAGLIARDINO JJ

Chicago, EEUU

Congreso; 67th Scientific Sessions American Diabetes Association; 2007

American Diabetes Association

We studied the transcription and immunocytochemical presence of Islet Neogenesis-Associated Protein (INGAP) and measured the binding in vivo of 125I-tyrosylated INGAP pentadecapeptide (125I-T-INGAP-PP) to different normal male hamster tissues. INGAP transcription (RT-PCR) and immunocytochemical expression (INGAP-positive cells) were assessed in hamster tissues. I125-T-INGAP-PP with our without T-INGAP-PP (0-1 mg/100 g bw) was injected and blood samples were drawn 5 and 60 min after injection. Radioactivity was measured in serum, brain, liver, kidney, small intestine, striated muscle, dorsal root ganglia and pancreas; results were expressed as the organ/serum ratio. We identified INGAP-positive cells and mRNA only in pancreatic islets and exocrine tissue. Radioactivity in serum samples increased from 0 (1,952 cpm/g serum) to 60 min (36,566 cpm/g serum). The simultaneous administration of T-INGAP-PP decreased this activity by 71% at 5, 10 and 20 min, but only by 9% at 60 min. Liver, pancreas and small intestine showed specific binding for 125I-T-INGAP-PP; the 50% displacement obtained with a 39.102 ng dose of T-INGAP-PP/100 g bw suggests the presence of a pancreatic receptor with low affinity for this peptide. We can conclude that INGAP transcription/expression is probably restricted to the pancreas where it would exert its effect in a paracrine fashion. INGAP would be released and circulate bound to a serum protein, and would bind to the liver for subsequent inactivation. INGAP binding to the small intestine would explain its immunocythochemical presence in this organ, where it would play a key role in the regulation of epithelial cell turnover.