GENDER DIFFERENCES IN THE METABOLIC RESPONSE TO GRADED NUMBERS OF TRANSPLANTED ISLETS OF LANGERHANS

Gender differences after treatment with streptozotocin (STZ) have been previously reported; however, differences in the glucose response to islet transplantation in STZ-induced diabetes in male and female rats after islet transplantation have not been examined. Male and female Wi star-Furth rats were made diabetic using STZ (55 mg/kg BW) and then gi ven an intraportal islet transplant. Control animals received sham inj ections and sham transplant surgery; diabetic animals received STZ and sham surgery. In male animals, islet grafts contained 0 (diabetic), 2 50, 500, 1000, 1500, 2000, and 3000 islets; in female rats, grafts wer e made up of 0, 500 700, 750, 1000, or 2500 islets. STZ treatment had more dramatic effects on male than female rats. During the diabetic ph ase, body weights of male rats were significantly reduced compared to those of control male animals; this was not observed among females. Al though all STZ-treated animals were hyperglycemic, plasma glucose leve ls in male diabetic rats were significantly higher than those in femal es during this phase (29.8 +/- 2.1 us. 24.6 +/- 0.6 mM). After islet t ransplantation, body weight gain was positively associated with the nu mber of islets transplanted in male rats (r(2) = 0.59; P < 0.01), but not in females (r(2) = 0.09; P > 0.8). In both male and female rats, a nimals that received 1000 islets or more were generally normoglycemic by 3 weeks posttransplant (males, 10.8 +/- 2.2 mM; females, 7.1 +/- 0. 2 mM). Approximately 60% of male and female animals that received 500 islets achieved a reduction in plasma glucose levels. Mean plasma gluc ose levels were 17.2 +/- 2.3 in the females and 22.6 +/- 1.0 mM in mal es. However, a significantly larger proportion of female 500-islet ani mals (6 of 16) achieved a plasma glucose level of 9.5 mM or less compa red with males receiving 500 islets (2 of 30). Multivariate regression analysis suggests that sex and islet number interact to affect glycem ic normalization after islet transplantation. Gender differences appea r to influence body weight and plasma glucose responses to islet trans plantation. This finding may have particular relevance when a marginal number of functional islets are available.