Chronic malnutrition impairs insulin sensitivity through both receptor and postreceptor defects in rats with mild...

The effect of coexisting chronic malnutrition on insulin sensitivity in mild diabetes was studied in rats. Food intake was restricted over an 8-week period to 50% of ad libitum intake by pair-feeding 4-week-old littermate rats injected with streptozocin ([STZ] 40 mg/kg intraperitoneally) at 8 weeks. Significantly greater glucose intolerance and hypoinsulinemia were seen in response to a glucose load in the malnourished diabetic group (P < .00005), suggesting that chronic malnutrition significantly accentuated beta-cell dysfunction from STZ. Significantly greater insulin resistance was also seen, with the percentage rate constant for glucose disappearance after a bolus of insulin being markedly impaired (P < .0001) in the malnourished diabetic group (1.5% +/- 0.2% x min-1 [SE]) compared with ad libitum-fed diabetic and normal rats (3.6% +/- 0.6% x min-1 and 4.7% +/- 0.7% x min-1, respectively; P < .01). Insulin binding to receptor in liver plasma membranes was altered by malnutrition (P < .00005), with the affinity of binding being significantly reduced compared with that of ad libitum-fed diabetic controls (P < .0001) at both the high-affinity site (3.9 +/- 0.2 v 13.7 +/- 3.3 x 10(-7) x mol/L-1) and low-affinity site (2.7 +/- 0.4 v 20.1 +/- 3.8 x 10(-5) x mol/L-1). During a constant glucose and insulin infusion (1.67 mU/kg/min), glucose clearance was significantly lower in malnourished rats (5.3 +/- 0.7 v 8.6 +/- 1.7 mL/gk/min, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)