Effect of INGAP-PP administration to nomal hamsters upon islet mass and B-cell function.

MADRID V; MAIZTEGUI B; BORELLI MI; DEL ZOTTO H; ALZUGARAY ME; GAGLIARDINO JJ

Helsingor, Dinamarca

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

European Association for the Study of Diabetes

Aim: To demonstrate whether the administration of a biologically active pentadecapeptide portion of islet neogenesis-associated protein (INGAP-PP) to normal hamsters can increase their â-cell mass without affecting metabolic homeostasis. Material and Methods: Normal hamsters were injected (i.p.) with INGAP-PP (500 ìg/day in two separate doses) (I) or saline (C) during 10 days. After this period we sacrificed the animals measuring body weight, serum glucose, triglyceride and insulin levels and removed the pancreas to study insulin secretion, islet DNA content and perform histological and morphometric analyses. Results: No differences were found between both groups (I vs.C) in either body weight, 109±5 vs.109±7 g; glycemia, 96±4 vs. 91±4 mg/dl; triglyceridemia, 204±12 vs. 171±33 mg/dl; and insulinemia 4±1 vs. 2±0.3 ng/ml, or glucose stimulated-insulin secretion in vitro. Conversely, INGAP-PP-treated hamsters showed a significant decrease in islet DNA content (0.07±0.002 vs. 0.1±0.01; p < 0.05) and a significant increase (p < 0.05) in  â-cell mass (6.6±0.04 vs. 4.1±0.7 mg), number of islet per unit area (2.8±0.3 vs.2.1±0.2 x106/µ2 ), extrainsular b-cells (2.3±0.5 vs.1.35±0.3x106/m2), percentage of islets in contact with ducts (77.±11 vs. 50±3.3 %) and â-cell replication rate (3.0±0.5 vs. 1.7±0.3%). INGAP-PP administration significantly decreased (p<0.05) islet size (6800±692 vs. 8083±785 m2) and INGAP-positive cells (130±62 vs.589±123/10 fields, x400). Conclusion: Our results suggest that INGAP-PP induces an increase in â-cell mass through a simultaneous increase in â-cell replication rate and neogenesis, and a negative feedback loop in endogenous INGAP cells which does not affect glucose and lipid homeostasis.