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

  • Nabeel A.J. Al-Hussary

    Student thesis: Doctoral ThesisDoctor of Philosophy


    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 Award1986
    Original languageEnglish


    • Insulin receptors
    • hypertension
    • Diabetes
    • obese mice
    • Guar gum

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