Transient hepatic response to glucagon in man: Role of insulin and hyperglycemia

E. Ferrannini, R. A. DeFronzo, R. S. Sherwin

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

We infused glucagon into normal humans with preventing changes in plasma glucose and insulin. Insulin (0.45 mU.min-1.kg-1) was infused for 90 min, while euglycemia was maintained by a variable glucose infusion. Subsequently, glucagon (6 ng.min-1.kg-1) was added, and changes in plasma glycose were avoided by appropriately reducing the glucose infusion. With insulin alone, glucose production (GP) fell to zero. When hyperglucagonemia (530 ± 32 pg.ml) was superimposed, GP rose promptly and then slowly declined. However, between 180 and 240 min, GP remained elevated (1.72 ± 0.30 mg.min-1.kg-1) as compard to an insulin control study (0.03 ± 0.20, P < 0.025). When hyperglycemia (+25 mg/100 ml) was induced between 180 and 240 min, glucagon-stimulated GP was completely suppressed. To determine whether this effect was mediated by hyperglycemia per se or glucose-induced hyperinsulinemia, between 180 and 240 min we increased either a) the insulin infusion (by 0.25 mU.min-1.kg-1) while maintaining euglycemia or b) plasma glucose (+25 mg/100 ml) while blocking insulin release with somatostatin. When the insulin was increased, GP declined by 68 ± 13% (P < 0.02). When plasma glucose alone was raised, GP fell from 1.44 ± 0.09 to 0.07 ± 0.16 mg.min-1.kg-1 (< 0.002). In conclusion, the hepatic response to sustained hyperglucagonemia is more persistent if changes in plasma glucose are prevented, and its transient nature is in part explained by a feedback adjustment to glucagon-induced hyperglycemia and hyperinsulinemia.

Original languageEnglish (US)
Pages (from-to)E73-E81
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume5
Issue number2
DOIs
StatePublished - Jan 1 1982
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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