Effect of INGAP-PP administration to normal hamsters upon islet mass and -cells function

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

Helsingor

Simposio; EASD Islet Study Group Symposium 2006; 2006

European Association for the Study of Diabetes (EASD)

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 beta-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  beta-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 beta-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 beta-cell replication rate (3.0±0.5 vs. 1.7±0.3%). INGAP-PP administration significantly decreased (p