Impact of lack of suppression of glucagon on glucose tolerance in humans

Pankaj Shah, Ananda Basu, R. Rita Basu, Robert A. Rizza

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

People with type 2 diabetes have defects in both α- and β-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a 'prandial' glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic (n = 10) or diabetic (n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng · kg-1 · min-1 beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the 'diabetic' insulin profile, lack of glucagon suppression resulted in a marked increase (P < 0.002) in both the peak glucose concentration (11.9 ± 0.4 vs. 8.9 ± 0.4 mmol/l) and the area above basal of glucose (927 ± 77 vs. 546 ± 112 mmol · l-1 · 6 h) because of impaired (P < 0.001) suppression of glucose production. In contrast, during the 'nondiabetic' insulin profile, lack of suppression of glucagon resulted in only a slight increase (P < 0.02) in the peak glucose concentration (9.1 ± 0.4 vs. 8.4 ± 0.3 mmol/l) and the area above basal of glucose (654 ± 146 vs. 488 ± 118 mmol · l-1 · 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

Original languageEnglish (US)
Pages (from-to)E283-E290
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume277
Issue number2 40-2
DOIs
StatePublished - Aug 1999

Keywords

  • Glucagon
  • Glucose disappearance
  • Glucose production
  • Insulin
  • Postprandial hypoglycemia
  • Type 2 diabetes

ASJC Scopus subject areas

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

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