Increased body fat in streptozotocin diabetic rats treated with intensive subcutaneous insulin therapy vs. islet transplantation.

The continued development of novel insulin treatment is predicated on the hypothesis that strict glycemic control is necessary to prevent the secondary complications of diabetes. Although dramatically successful in reducing selected secondary complications, intensive insulin therapy has consequences. These include hypoglycemia, weight gain, and body fat accumulation. In the present studies we compared a model of intensive insulin therapy in diabetic rats and contrasted weight gain and body fat accumulation with pancreatic islet transplantation. Female Wistar Furth rats (173 g) administered streptozotocin (55 mg x kg(-1), iv) remained diabetic (DB) for four or nine weeks. At week three, a third group was transplanted (TRAN) with islets of Langerhans (3519 +/- 838 150 microm islets); one week later group four began intensive subcutaneous insulin therapy (ISIT; 4 x 0.5-1.0 U regular insulin x day(-1)). Within one week ISIT rats had normalized plasma glucose; levels were not different from age matched controls (CN) or TRAN animals (ISIT 10.6 +/- 1.7, CN 7.2 +/- 0.4, TRAN 7.7 +/- 0.8 mmol x L(-1), P > 0.05). The cumulative occurrence of one episode of hypoglycemia (< 2.8 mmol x L(-1)) occurred in 50% of ISIT rats. At study termination, body weight of ISIT and CN rats did not differ (199 +/- 4 vs. 207 +/- 3, P > 0.05). While carcass protein content was similar for TRAN, ISIT, and CN animals, the body fat of ISIT animals was 24% greater than in CN rats and 21% greater than in TRAN rats (P < 0.05). Correlation of body fat vs. plasma glucose illustrated hypoglycemia contributed to the body fat gain of ISIT rats (n = 8, r = -0.70, P = 0.0535). These studies illustrate a disproportionate gain of body fat from ISIT, an effect not observed with islet transplantation. Thus, the metabolic benefit ascribed to islet transplantation appears related to the absence of hypoglycemia.

Pancreatic islet transplantation improves body composition, decreases energy intake and normalizes energy efficiency in previously diabetic female rats.

We investigated the weight gain, body composition, and feed efficiency of female Wistar Furth rats (170 +/- 1 g) made diabetic with streptozotocin (55 mg/kg intravenously), then infused intraportally with 3519 +/- 838 (150 mu equivalent units) syngeneic pancreatic islets of Langerhans. After islet transplants (5-6 wk), nutritional energetics were evaluated in transplanted rats (Transplant), and also in 3- and 9-wk diabetic (Diab-3, 9) and control rats treated with sham infusions and similar surgical manipulations (Sham-3, 9). Diabetic rats demonstrated marked hyperphagia, which was corrected by islet transplantation (577 +/- 53 vs. 266 +/- 19 kJ/d; P < 0.0001) and was not different than sham control rats (285 +/- 24 kJ/d; P > 0.05). Three weeks of diabetes resulted in a lower protein (Diab-3, 24.8 +/- 2.6 g vs. Sham-3, 30.9 +/- 1.0 g) and fat content (1.9 +/- 0.8 g vs. 11.6 +/- 1.7 g) in the rats' carcasses. However, 6 wk after islet transplantation, rats receiving islets (Transplant) were not different than control rats (Sham-9) (31.9 +/- 1.7 g vs. 33.3 +/- 1.9 g protein and 15.4 +/- 3.0 g vs. 15.1 +/- 3.2 g fat). Three weeks of diabetes resulted in a lesser energy efficiency compared with Sham rats (2.7 +/- 2.0 vs. 7.1 +/- 1.9 kJ gained/100 kJ ingested); islet-transplanted rats were not different than Sham-9 rats (4.9 +/- 2.3 vs. 4.7 +/- 1.4 kJ gained/100 kJ ingested). These data illustrate that islet transplantation in previously diabetic female rats improves growth with proportional gains in body protein and fat mass. This is modulated in part by a reduced food intake and an energy efficiency that is improved relative to controls. These studies offer an optimistic outlook for the continued development of more physiological insulin delivery strategies that preclude the nutritional complications associated with exogenous insulin administration.