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

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

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52 Scopus citations


We infused glucagon into normal humans with preventing changes in plasma glucose and insulin. Insulin (0.45 was infused for 90 min, while euglycemia was maintained by a variable glucose infusion. Subsequently, glucagon (6 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 was superimposed, GP rose promptly and then slowly declined. However, between 180 and 240 min, GP remained elevated (1.72 ± 0.30 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 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 (< 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
Issue number2
StatePublished - 1982
Externally publishedYes

ASJC Scopus subject areas

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


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