Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM

S. Dinneen, A. Alzaid, D. Turk, R. Rizza

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


Carbohydrate ingestion results in a fall in glucagon concentration in non-diabetic but not in diabetic individuals. To determine if, and the mechanism by which, lack of postprandial suppression of glucagon contributes to hyperglycaemia, nine subjects with insulin-dependent diabetes mellitus (IDDM) ingested 50 g of glucose containing both [2-3H] glucose and [6-3H] glucose on two occasions. [6-14C] glucose, insulin and low-dose somatostatin were infused intravenously at the same rates on both occasions. A basal glucagon infusion was started either at the same time ("constant glucagon") or 2 h following ("suppressed glucagon") glucose ingestion. This resulted in lower (p<0.001) glucagon concentrations during the first 2 h of the suppressed than during the constant glucagon study days (63±1 vs 108±2 pg/ ml). Lack of suppression of glucagon led to higher (p<0.01) postprandial glucose concentrations (10.3±0.9 vs 8.1±0.7 mmol/l) and a greater (p<0.02) integrated glycaemic response. The excessive rise in glucose was due to higher (p<0.02) rates of postprandial hepatic glucose release during the constant than during the suppressed glucagon study days, whether measured using either [6-3H] glucose (2.6±0.2 vs 2.0±0.2 mmol·kg-1 per 6 h) or [2-3H] glucose (3.0±0.3 vs 2.4±0.2 mmol·kg-1 per 6 h) as the meal tracer. Glucose disappearance, initial splanchnic glucose clearance and hepatic glucose cycling did not differ on the two occasions. Thus, the present studies demonstrate that lack of postprandial suppression of glucagon, by increasing hepatic glucose release, contributes to hyperglycaemia in subjects with IDDM.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
Issue number3
StatePublished - Mar 1995


  • Hepatic glucose release
  • glucose/glucose 6-phosphate cycling
  • hepatic glucose cycling
  • insulin-dependent diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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