Endocrine Abstracts

Insulin resistance is associated with obesity, metabolic syndrome and hypertension. These risk factors for type 2 diabetes and cardiovascular disease may be programmed by the early diet. Previous studies have shown poor insulin sensitivity in obese relative to lean sheep. Here, we considered whether insulin sensitivity in pre- and postnatally nutritionally challenged sheep offspring was due to changes at the pancreatic level. Thirty-six twin-bearing ewes were randomly allocated to receive either a control (C, n=24) or nutrient restricted diet (NR, 50% C intake, n=12) from days 30 to 80 of gestation. Thereafter all sheep were fed to 100% requirement to term (12–13 MJ/day). Offspring were delivered spontaneously and either ewe reared (C, n=8 from control group) or formula-fed (FF, n=8 from control group; 1–1.5 L/d Volac) until weaning (10–12 weeks). Thereafter to 1 year offspring were reared indoors with restricted activity and increased food availability to promote fat deposition (obese controls OC, n=8; obese nutrient restricted ONR, n=12; obese bottle-fed OBF, n=8) or pasture grazed with unrestricted activity (Lean controls LC, n=8). Five micrometer sections of pancreas were stained for insulin and glucagon using standard DAB immunohistochemical protocols, and percentage staining in the Islets of Langerhans was analysed using Image Pro software. There were no effects of diet on insulin, however males had significantly higher levels than females (37.1±3.3 vs 29.4±2.5%). There were no main effects of diet or gender on glucagon, but interactions between group and gender showed ONR males had significantly higher glucagon than all other groups (male ONR, 12.2±2.5 versus male OC, 4.4±1.6). To conclude, this study has shown no evidence of developmental programming of insulin at the level of the pancreas, however there is evidence of programming of glucagon in males only, suggesting sex-specific mechanisms may be responsible.