Comparison of the suppressive effects of elevated plasma glucose and free fatty acid levels on glucagon secretion in normal and insulin-dependent diabetic subjects. Evidence for selective alpha-cell insensitivity to glucose in diabetes mellitus

J Clin Invest. 1976 Aug;58(2):320-5. doi: 10.1172/JCI108475.


To examine whether abnormal pancreatic alpha-cell function found in human diabetes mellitus may represent a selective insensitivity to glucose, plasma glucagon responses to hyperglycemia and elevation of plasma free fatty acid levels (both known suppressors of glucagon secretion) were compared in juvenile-onset, insulin-requiring diabetic subjects, and in normal nondiabetic subjects. In the latter, both elevation of plasma free fatty acid levels induced by heparin administration of hyperglycemia produced by intravenous infusion of glucose resulted in a comparable 30--40% suppression of circulating glucagon levels (P less than 0.01). In the diabetic subjects, glucagon suppression by hyperglycemia (less than 20%) was less than that occurring in normal subjects (P less than 0.01), even when accompanied by infusion of supraphysiologic amounts of insulin. However, suppression of glucagon levels by elevation of plasma free fatty acids in the diabetic group was similar to that found in normal subjects and of comparable magnitude to that due to hyperglycemia in the normal subjects. These results thus demonstrate a selective impairment of the diabetic alpha-cell response to glucose and provide further evidence for the presence of an abnormal alpha-cell glucoreceptor in human diabetes mellitus.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Blood Glucose / physiology
  • Clinical Trials as Topic
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / physiopathology*
  • Diabetes Mellitus, Type 1 / blood
  • Fatty Acids, Nonesterified / blood*
  • Female
  • Glucagon / blood*
  • Glucagon / metabolism
  • Humans
  • Hyperglycemia / blood*
  • Insulin / therapeutic use
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology*
  • Male
  • Receptors, Drug


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Receptors, Drug
  • Glucagon