title: Chronic sodium-retaining action of insulin in diabetic dogs.
abstract: Insulin-mediated sodium retention is implicated as a mechanism for hypertension in metabolic syndrome and type II diabetes. However, there is no direct experimental evidence for a sustained antinatriuretic effect of insulin outside of rodents, and all previous studies in dogs have been negative. This study used a novel approach to test for a chronic sodium-retaining action of insulin in dogs, by testing the hypothesis that natriuresis in type I diabetes is dependent on the decrease in insulin, rather than being due solely to osmotic actions of hyperglycemia. Dogs were chronically instrumented and housed in metabolic cages. Fasting blood glucose in alloxan-treated dogs was maintained at ~65 mg/dl by continuous intravenous insulin infusion. Then, a 6-day diabetic period was induced by either 1) decreasing the insulin infusion to induce type I diabetes (D; blood glucose = 449 ± 40 mg/dl) or 2) clamping the insulin infusion and infusing glucose continuously (DG; blood glucose = 470 ± 56 mg/dl). Control urinary sodium excretion (UnaV) averaged 70 ± 5 (D) and 69 ± 5 (DG) meq/day and increased on day 1 in both groups. UnaV remained elevated in the D group (115 ± 15 meq/day days 2-6), but it returned to control in the DG group (69 ± 11 meq/day days 2-6) and was accompanied by decreased lithium clearance. Thus, insulin had a sustained antinatriuretic action that was triggered by increased glucose, and it was powerful enough to completely block the natriuresis caused by hyperglycemia. These data may reveal an unrecognized physiologic function of insulin as a protector against hyperglycemia-induced salt wasting in diabetes.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.
authors.forename: M Marlina
authors.initials: MM
authors.lastname: Manhiani
authors.forename: Michael T
authors.initials: MT
authors.lastname: Cormican
authors.forename: Michael W
authors.initials: MW
authors.lastname: Brands
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004285:Dogs; D006943:Hyperglycemia / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011897:Random Allocation; D012964:Sodium / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012964:Sodium