CENEXA   05419
CENTRO DE ENDOCRINOLOGIA EXPERIMENTAL Y APLICADA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of Islet Neogenesis-Associated Protein Pentadecapeptide (INGAP-PP) on Islet Mass and Function in Normal Hamsters
Autor/es:
DEL ZOTTO H; MADRID V; MAIZTEGUI B,; ALZUGARAY E; BORELLI I; GAGLIARDINO J
Lugar:
Chicago, EEUU
Reunión:
Congreso; 67th Scientific Sessions American Diabetes Association; 2007
Institución organizadora:
American Diabetes Association
Resumen:
We investigated the effect of a pentadecapeptide of Islet Neogenesis-Associated Protein (INGAP-PP) containing the biologically active portion of INGAP, on B-cell mass and metabolic homeostasis of normal hamsters. We administered INGAP-PP (500 µg/day ip at two daily doses) (T) or saline solution (C) to normal hamsters during 10 days. We measured body weight, glycemia (G), triglyceridemia (TG) and insulinemia (I) at the moment of sacrifice and then extracted pancreases to isolate islets by collagenase digestion. Islets were incubated with different glucose concentrations, measuring insulin secretion and DNA content. Pancreatic morphological changes were quantified by immunocytochemistry and morphometry. We found no significant differences (T vs. C) either in body weight (109 ± 5 vs. 109 ± 7 g), G (96 ± 4 vs. 91 ± 4 mg/dl), TG (204 ± 12 vs. 171 ± 33 mg/dl) and I (4 ± 1 vs. 2 ± 0.3 ng/ml), or glucose-induced insulin secretion. However, INGAP-PP-treated hamsters showed a marked increase (P < 0.05) in B-cell mass (6.6 ± 0.04 vs. 4.1 ± 0.7 mg), number of islets/µ2 (2.8 ± 0.3 vs. 2.1 ± 0.2 x 106/µ2) and extrainsular B cells (2.3 ± 0.5 vs.1.35 ± 0.3 x 106/µ2), percent of islets in contact with ducts (77 ± 11 vs. 50 ± 3.3 %) and B-cell replication rate (3.0 ± 0.5 vs. 1.7 ± 0.3 %). In T hamsters, islet size (6800 ± 692 vs. 8083 ± 785 µ2), islet DNA content (0.07 ± 0.002 vs. 0.1 ± 0.01) and number of INGAP-positive cells (130 ± 62 vs.589 ± 123/10 fields, x 400) decreased significantly (P<0.05). These results suggest that INGAP-PP induces an increase in B-cell mass through the simultaneous increase of its apoptotic and neogenesis rate, and a negative feedback in endogenous INGAP-positive cells. The newly formed B-cells would keep their insulin secretion regulatory mechanism intact, without affecting metabolic homeostasis.