Sucrose Administration to Normal Hamsters Induces Simultaneous Changes in Islet Neogenesis and INGAP-Positive Cell Mass

Sucrose Administration to Normal Hamsters Induces Simultaneous Changes in Islet Neogenesis and INGAP-Positive Cell Mass – Abstract

Juan J Gagliardino

We have previously shown that sucrose administration to normal rats and hamsters induces pancreatic growth and islet neogenesis. The factors involved in this process are unknown. Islet neogenesis associated protein (INGAP) is a putative islet cell growth and differentiation factor whose expression is stimulated by experimentally induced islet neogenesis. We hypothesized that INGAP is involved in the sucrose- induced islet cell growth and differentiation. This study examined the changes in islet neogenesis and INGAP-positive cell mass induced by administration of 10% sucrose to male Syrian golden hamsters for 8 (S8) or 24 (S24) weeks. Differences were analyzed by quantitative immunohistochemistry. BrdU index, [Beta]-cell mass, [Beta]-cell size and the number of islets/area were significantly higher in S8 versus (vs) control (C) hamsters. In contrast, islet volume was smaller in S8 vs C8. The differences in S24 compared to C24 were not significant. INGAP-positive cell mass was significantly larger in S8 vs C8 hamsters, but not in S24 vs C24 animals. In both C and S animals most INGAP-positive cells were located in the islet periphery. However, a small percentage was detected in acinar and ductal cells. INGAP-positive cells coexpressed glucagon in different proportions according to their location and the type of treatment received. The percentage of cells coexpressing INGAP and glucagon in C8 vs. S8 are as follows: in the islet periphery, 47% vs. 31%; in ductal cells 16% vs. 6%; and in acinar cells 17% vs. 33%. INGAP-positive cells in the islets also coexpressed cytokeratins (ductal markers) only in S8 animals. We conclude that sucrose administration to normal hamsters causes neogenesis at 8 weeks which correlates with an increase in INGAP-positive cell mass of extrainsular origin, commencing with initial glucagon-cell differentiation. This process is complete at 24 weeks. These data suggest that INGAP might play a role in islet neogenesis and thus could become a tool to treat conditions in which [Beta]-cell replacement is necessary.

JUAN J GAGLIARDINO, HECTOR DEL ZOTTO, LAURA MASSA, RONIT RAFAELOFF-PHAIL, ANNE REIFEL-MILLER, GERALD GOLD, AARON I VINIK, La Plata, Argentina

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