Insulin Receptor Binding in Hypertension and Non-Insulin Dependent Diabetes Mellitus

Abstract

Human erythrocyte and mouse adipocyte insulin receptor binding assays have been used to quantify insulin receptor binding in mild hypertensive patients with and without non-insulin dependent diabetes and obese mice. In normal male volunteers erythrocyte insulin receptor binding was not affected by a 12 hr overnight fast. Treatment of mildly hypertensive non-diabetic patients with bendrofluazide increased erythrocyte insulin receptor concentration after only one month without producing a significant deterioration in glucose tolerance. In mildly hypertensive diabetic patients, bendrofluazide treatment caused a significant aggravation in glucose intolerance after 4 months with little effect on insulin receptor binding. This may have been the result of hypokalaemia since bendrofluazide with potassium supplementation significantly increased the insulin receptor concentration in this group. Treatment with nifedipine neither precipitated glucose intolerance in non-diabetic patients nor aggravated the glucose intolerance of diabetic patients. Indeed, there was a paradoxical increase in serum insulin levels in both groups of patients. Guarem treatment of non-insulin dependent diabetics lowered plasma glucose and insulin levels and marginally improved glucose tolerance without influencing erythrocyte insulin receptor binding. High doses of guarem lowered the plasma glucose, insulin and body weight of obese mice. Only a high dose of guarem significantly increased adipocyte insulin receptor affinity which became evident after 48 hours. In obese mice starvation probably caused the improvement in glycaemia observed in response to guarem treatment. Adipocyte insulin receptor concentration and both basal and insulin stimulated rates of glucose oxidation were significantly reduced in obese mice compared with lean suggesting that defects in adipose tissue insulin receptor binding and insulin action may be primary aetiological factors in the insulin resistance of obese mice. Differences in insulin receptor concentration and affinity but not insulin action have been demonstrated in abdominal and subcutaneous fat from obese mice.