ISLET TRANSPLANTATION REVERSES CARCASS PROTEIN LOSS IN DIABETIC RATS WITHOUT INDUCING DISPROPORTIONATE FAT ACCUMULATION

The Diabetes Control and Complications Trial demonstrated that intensi ve insulin therapy (IIT) improves many secondary complications of insu lin-dependent diabetes mellitus. However, weight gain in IIT is associ ated with increased body fat, and no improvement in lean body mass. In the present study we investigated the effects of experimental diabete s on changes in body composition and probed the benefit of glycaemic c ontrol achieved through islet transplantation. Male Wistar Furth rats (weight 273+/-9 g) made diabetic for 2 weeks with streptozotocin (55 m g/kg) were infused intraportally with 3265+/-692 (150 mu m islet equiv alent units) syngeneic islets of Langerhans. Body composition was eval uated by proximate analysis in carcasses of transplant rats (Trans), a nd also in rats made diabetic for 2 or 7 weeks (Db-2, Db-7) and in 2- and 7-week sham controls (Sham-2, Sham-7). Fed plasma glucose levels w ere 7.3+/-1.1, 28.2+/-2.4, 26.8+/-3.9, 7.5+/-1.0 and 7.0+/-0.1 mm/l, r espectively, and neither glucose tolerance nor fasting plasma insulin differed between control vs transplant rats (p > 0.05). Two weeks of d iabetes resulted in a body weight 82% of that of controls (240+/-5 vs 292+/-8 g, p < 0.05) and 5 subsequent weeks of diabetes further suppre ssed growth by an additional 12% (p < 0.05). Five weeks following isle t transplantation, islet-transplant rats had regained lost weight and were not significantly different from control animals (274+/-19 vs 291 +/-21 g, p > 0.05). Body composition analysis indicated that protein m ass was virtually completely regained by 5 weeks post-transplantation (Db-2 = 39.6+/-0.9, Trans = 46.8+/-4.7, Sham-7 = 49.6+/-2.9 g; p > 0.0 5: Trans vs Sham-7), and fat mass of transplant rats was 75% that of c ontrol values (p < 0.05). These data illustrate that the near physiolo gic glycaemic control achieved through pancreatic islet transplantatio n is associated with normalization of lean body mass accretion in expe rimental diabetes and does not induce a disproportionate accumulation of body fat.