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.

Date of Award	May 1986
Original language	English
Awarding Institution	Aston University