Effects of food restriction and insulin treatment on (Ca2+ + Mg2+)-ATPase response to insulin in kidney basolateral membranes of noninsulin-dependent diabetic rats☆

Insulin increases (Ca2+ + Mg2+)-ATPase activity in cell membranes of normal rats but fails to do so in membranes of non-insulin-dependent diabetic (NIDD) rats. The loss of regulatory effect of the hormone on the enzyme might contribute to the insulin resistance observed in the NIDD animals. To further test this hypothesis, the effects of insulin treatment and acute food restriction on the ability of insulin to regulate the ATPase activity in kidney basolateral membranes (BLM) of NIDD rats were studied. Although insulin levels in NIDD and control rats were similar, plasma glucose was higher in the NIDD rats (18.3 ± 1.5 v 19.3 ± 1.7 μU/mL and 236 ± 32 v 145 ± 3 mg/dL, respectively). Insulin treatment (2 U100 g), which increased plasma insulin in the NIDD rats (47.8 ± 11.5 μU/mL; P < .05), did not decrease their glucose (221 ± 25 mg/dL). Higher insulin dose (4 U100 g) decreased glucose level in the NIDD rats (73 ± 3 mg/dL; P < .001) but increased their plasma insulin 10-fold (202.5 ± 52.5 μU/mL). Acute food restriction decreased glucose levels in the NIDD rats to levels seen in controls (135 ± 3 mg/dL), while their insulin decreased by half (8.5 ± 1.0 μU/mL; P < .05). Basal (Ca2+ + Mg2+)-ATPase activity in BLM of all diabetic rats was higher than in controls (P < .05). None of the treatments reversed this defect. Insulin (12.5 to 200 μU/mL) increased the ATPase activity (10% to 40%) in BLM from controls but not from NIDD rats. In BLM from food-restricted diabetic rats, insulin increased the enzyme activity by 16% to 42%, but the dose-response curve was shifted to the right. In BLM from insulin-treated rats, insulin caused a slight (10% to 20%) increase in enzyme activity only at its highest concentration (200 μU/mL). These findings confirm the existence of insulin resistance in the NIDD rats and reveal that acute food restriction ameliorates it. The amelioration of insulin resistance was accompanied by a regained ability of insulin to regulate the membrane (Ca2+ + Mg2+)-ATPase. It is suggested that part of the beneficial effect of food restriction on insulin resistance in the NIDD rat is due to a restoration of insulin's ability to regulate cell Ca2+ homeostasis.