Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM.
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.
Dinneen
S
S
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Alzaid
A
A
Turk
D
D
Rizza
R
R
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004040:Dietary Carbohydrates; D004435:Eating; D005260:Female; D005934:Glucagon / Q000008:administration & dosage; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011168:Portal System; D011865:Radioisotope Dilution Technique; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D004040:Dietary Carbohydrates; D007328:Insulin; D014316:Tritium; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose