Transcription, expression and tissue binding in vivo of INGAP and INGAP-related peptide in normal hamsters

Abstract

We studied islet neogenesis-associated protein (INGAP) transcription and its immunocytochemical presence in and binding in vivo of 125I-tyrosylated INGAP pentadecapeptide ( 125I-T-INGAP-PP) to different normal male hamster tissues. 125I-T-INGAP-PP was injected intraperitoneally with or without unlabeled T-INGAP-PP (0–1 mg/100 g bw), drawing blood samples at different times after injection; radioactivity was measured in serum, brain, skeletal muscle, dorsal root ganglia, liver, kidney, small intestine and pancreas samples, expressing results as organ:serum ratio. INGAP transcription (RT-PCR) and immunopositive cells were investigated in liver, kidney, brain, small intestine and pancreas. Total serum radioactivity increased progressively as a function of time; whereas 71% of this activity was displaced by unlabeled T-INGAP-PP at 5, 10 and 20 min, only 9% was at 60 min. Only liver, pancreas and small intestine specifically bound 125I-T-INGAP-PP. The pancreas tissue dose–response curve showed a 50% displacement at 3.9 × 10 4 ng/100 g bw, suggesting a low binding affinity of its receptor. INGAP-mRNA was only identified in pancreatic islets and exocrine tissue. Our results suggest that INGAP transcription/expression is probably restricted to pancreas cells exerting its effect in a paracrine fashion. INGAP would be released and circulate bound to a serum protein from where it is bound and inactivated by the liver. Tissue binding could also explain INGAP's immunocytochemical presence in small intestine, where it could affect epithelial cell turnover.