Insulin resistance, insulin deficiency, and non-insulin-dependent diabetes mellitus.
Recent information suggests that type 2 diabetes mellitus (NIDDM) is associated with severe insulin resistance, but other information suggests that there is a hypoinsulinemic state. To investigate the nature of the insulin resistance, 10 newly diagnosed, mildly obese type 2 diabetics and 11 long-standing type 2 diabetics with secondary failure to sulfonylureas were studied. Insulin was given by continuous subcutaneous infusion (CSII) for two weeks. CSII produced near-normoglycemia after 1-4 days in all patients with modest amounts of insulin (0.5-0.9 U/kg/24 h). These results demonstrate that whatever insulin resistance prevails in NIDDM, it does not prevent induction of normoglycemia by insulin. This suggests that either the insulin resistance is a secondary event caused by hyperglycaemia, or that NIDDM patients are hypoinsulinemic. In further studies in vitro, the effect of glucose on the rate of glycolytic glucose utilization by isolated rat soleus muscle and on hexose transport in rat skeletal myocyte line L8 were assessed. In the first case, an increase in glucose concentration led to a decrease in muscle glycolysis, and in the second case a hyperglycemic concentration of glucose led to a marked reduction in hexose transport, which was fully reversible within two hours. The clinical and in vitro results plus literature data suggest that insulin resistance can be overcome by insulin in NIDDM, and that beta-cell responsiveness to glucose is greatly reduced in NIDDM, but the defect is restricted to the acute stimulatory phase of glucose induction of insulin release. If this defect can be corrected, acute insulin release will occur so that NIDDM would be cured notwithstanding the existence of insulin resistance.
Cerasi
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Department of Endocrinology and Metabolism, Hebrew University Hadassah Medical Center, Jerusalem, Israel.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin