Chronic Undernutrition Accentuates Insulin Deficiency in Rats With Mild Streptozocin-Induced Diabetes

The effect of chronic undernutrition on coexisting diabetes mellitus was studied in pair-fed littermate rats with mild streptozocin-induced diabetes. They were either fed adlibitum or 50% food restricted for 9 wk. Undernourished diabetic rats, in which weight gain was reduced by 40%, had significantly higher glucose intolerance (mean ± SE, fractional rate of glucose disappearance during glucose tolerance test [K_gtt] 1.77 ± 0.16) than diabetic littermates fed ad libitum(2.33 ± 0.21, P < 0.05) or nondiabetic controls (3.8 ± 0.7, P < 0.01). The total area under the insulin response curve was significantly reduced in both groups of diabetic rats, but the undernourished group showed a 45% greater reduction in overall secretion than normally nourished diabetic littermates (21.3 ± 2.7 vs. 39.4 ± 6.3 nM · min in the diabetic group, P < 0.01, and 65.7 ± 6.1 nM · min in controls). There was also a marked reduction in first-phase insulin secretion in the undernourished rats (4.75 ± 0.24 vs. 9.84 ± 1.36 nM, P < 0.05, and 14.3 ± 1.8 nM, P < 0.01, respectively, in normally nourished diabetic littermates and controls). After refeeding, a significant improvement occurred in K_gtt (to 2.67 ± 0.24, P < 0.01) and first-phase insulin secretion (to 9.69 ± 1.65 nM, P < 0.05). The postrefeeding values were not different from those in the normally nourished diabetic littermates, indicating that the effect wasfully reversible and solely attributable to undernutrition rather than to enhanced β-cell cytotoxicity from streptozocin. It is concluded that chronic malnutrition accentuates β-cell dysfunction in rats with mild streptozocin-induced diabetes, indicating that its effects can amplify the deficits induced by another diabetogenic influence. This may be important in elderly diabetic individuals who are often undernourished. It may also contribute to the insulinopenia observed in malnutrition-related diabetes mellitus.