Circulating insulin inhibits glucagon secretion induced by arginine in type 1 diabetes

Eur J Endocrinol. 2000 Jan;142(1):30-4. doi: 10.1530/eje.0.1420030.

Abstract

Objective: To evaluate if insulin has a suppressive effect on the glucagon secretion stimulated by arginine in type 1 diabetes.

Research design and methods: The alpha-cell response to an i.v. bolus of arginine (150mgkg(-1)) followed by an infusion of arginine (10mgkg(-1)min(-1)) was studied in random order during either low dose infusion (LDT) or high dose infusion (HDT) of insulin in ten patients with type 1 diabetes. The blood glucose level was clamped at an arterialized level of 5mmoll(-1) by a variable infusion of glucose. Venous C-peptide, glucagon, growth hormone, and insulin were analyzed.

Results: The mean plasma concentration of insulin was four times higher during the HDT. The C-peptide level did not differ between the LDT and the HDT. During the LDT in response to arginine the blood glucose level increased from 5.0 to 5.8mmol l(-1) although the glucose infusion was markedly reduced, while no change was seen during the HDT. A significantly smaller increase in the glucagon levels during the HDT was seen (area under the curve of 413+/-45 vs 466+/-44pgml(-1)h(-1), P=0.03) while the growth hormone levels were almost identical.

Conclusion: This study demonstrates that a high level of circulating insulin exerts an inhibitory effect on the glucagon response to arginine in type 1 diabetes. Thus, the suppressive effect of insulin on the glucagon release from the alpha-cell seems to be general and not only dependent on stimulation by hypoglycemia.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arginine / pharmacology*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon / antagonists & inhibitors*
  • Glucagon / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / blood*
  • Infusions, Intravenous
  • Insulin / administration & dosage*
  • Insulin / blood*
  • Male
  • Middle Aged
  • Pancreas / cytology
  • Pancreas / metabolism

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Glucagon
  • Arginine