We determined alterations in renal aquaporin-2 (AQP2) gene expression in association with impaired water excretion in glucocorticoid-deficient rats. After adrenalectomy, Sprague-Dawley rats were administered aldosterone alone by osmotic pumps (glucocorticoid-deficient rats). As a control, both aldosterone and dexamethasone were administered. These animals were subjected to the studies on days 7-14. The expressions of AQP2 mRNA and protein in kidney of the glucocorticoid-deficient rats were increased by 1.6- and 1.4-fold compared with the control rats, respectively. An acute oral water load test verified the marked impairment in water excretion in the glucocorticoid-deficient rats. One hour after the water load, the expressions of AQP2 mRNA and protein were significantly reduced in the control rats, but they remained unchanged in the glucocorticoid-deficient rats. However, there was no alteration in [(3)H]arginine vasopressin (AVP) receptor binding and AVP V(2) receptor mRNA expression in the glucocorticoid-deficient rats. A V(2)-receptor antagonist abolished the increased expressions of AQP2 mRNA and protein in the glucocorticoid-deficient rats. These results indicate that augmented expression of AQP2 participates in impaired water excretion, dependent on AVP, in glucocorticoid deficiency.

These results indicate that the attenuated regulation of the AQP-2 gene leads to the decrease in urinary concentrating ability in the experimental SIADH rats, suffering from hypervolemic state, compared with the normonatremic rats receiving AVP. Either hypervolemia or hypotonicity may diminish the post-receptor signaling of AVP in renal collecting duct cells, under the chronic AVP excess state found in SIADH.

Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese type 2 diabetic patients. Four patients were treated with sulfonylureas, and the remaining seven with diet therapy alone. None had diabetic retinopathy and microalbuminuria. Their fasting glucose level was 117+/-7 mg/dl (mean +/- SE), and HbA1c was 6.6+/-0.3%. Age-, sex-, and BMI-matched subjects with normal glucose tolerance served as control subjects. Plasma insulin response to the stimuli and insulin sensitivity indexes (S(I), S(I)*, and S(I)2* were derived from a minimal model and single- and two-compartment-labeled minimal models) were impaired in the type 2 diabetic patients. The combined ability of glucose, per se, to increase its own uptake and suppress EGP (glucose effectiveness [SG]), which was derived from kinetic analysis of plasma glucose by a minimal model, was significantly lower in the type 2 diabetic patients (0.0132+/-0.0015 vs. 0.0203+/-0.0022; P<0.05). However, the ability of glucose, per se, to stimulate glucose uptake, assessed as S(G)* and S(G)2* from the kinetic analysis of labeled glucose by single- and two-compartment minimal model, was not impaired in those patients. EGP of the type 2 diabetic patients as a whole was suppressed to the level similar to that of the control subjects despite a higher plasma glucose level throughout FSIGT. When EGP in the diabetic subjects was analyzed, considering their recent glycemic control, the initial suppression was blunted in the patients with higher HbA1c levels. In conclusion, glucose mass action to stimulate glucose uptake remains near-normal in the lean Japanese type 2 diabetic patients of this study, whereas ability of glucose to suppress EGP is impaired in the patients with recent hyperglycemia. This blunted suppression of EGP might be one of the conspirators for decreased S(G) in subjects with type 2 diabetes.

Abstract.It has been reported that there is an inverse relationship between serum sodium (Na) and potassium (K) levels in patients with diabetic coma. The present study was undertaken to determine whether such an inverse relation depends upon plasma glucose levels in diabetic patients for their glycemic control. We examined two hundred and fifty-two patients with diabetes mellitus admitted to our hospital during the one-year period to control their plasma glucose levels, except for those having nephropathy or liver dysfunction. Serum Na and K, plasma glucose, and serum and urinary C-peptide levels were determined.There was a negative correlation between serum Na levels and fasting plasma glucose (FPG), and, conversely, a positive correlation between serum K levels and FPG. The changes were more evident in the patients with insulin-dependent diabetes mellitus than those with non-insulindependent diabetes mellitus.There was an inverse relation between serum Na and K levels and it was profoundly dependent upon plasma glucose levels in all the diabetic patients before tight control of their glycemic levels. The disorder may be based on the movement of electrolytes between intra-and extracellular spaces, dependent on the impaired insulin action as well as hyperosmolality.

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