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Effect of Glucagon-Like Peptide-1(7-36)-Amide on Initial Splanchnic Glucose Uptake and Insulin Action in Humans With Type 1 Diabetes

¹ Department of Internal Medicine, Division of Endocrinology, Metabolism, and Nutrition, and the
² Department of Internal Medicine, Division of Gastroenterology, Mayo Clinic and Foundation, Rochester, Minnesota
³ Department of Medical Physiology, The Panum Institute, Copenhagen, Denmark

In vitro studies indicate that glucagon-like peptide-1(7-36)-amide (GLP-1) can enhance hepatic glucose uptake. To determine whether GLP-1 increases splanchnic glucose uptake in humans, we studied seven subjects with type 1 diabetes on two occasions. On both occasions, glucose was maintained at 5.5 mmol/l during the night using a variable insulin infusion. On the morning of the study, a somatostatin, glucagon, and growth hormone infusion was started to maintain basal hormone levels. Glucose (containing [³H]glucose) was infused via an intraduodenal tube at a rate of 20 µmol · kg^-1 · min^-1. Insulin concentrations were increased to 500 pmol/l while glucose was clamped at 8.8 mmol/l for the next 4 h by means of a variable intravenous glucose infusion labeled with [6,6-²H₂]glucose. Surprisingly, the systemic appearance of intraduodenally infused glucose was higher (P = 0.01) during GLP-1 infusion than saline infusion, indicating a lower (P < 0.05) rate of initial splanchnic glucose uptake (1.4 ± 1.5 vs. 4.8 ± 0.8 µmol · kg^-1 · min^-1). On the other hand, flux through the hepatic uridine-diphosphate–glucose pool did not differ between study days (14.2 ± 5.5 vs. 13.0 ± 4.2 µmol · kg^-1 · min^-1), implying equivalent rates of glycogen synthesis. GLP-1 also impaired (P < 0.05) insulin-induced suppression of endogenous glucose production (6.9 ± 2.9 vs. 1.3 ± 1.4 µmol · kg^-1 · min^-1), but caused a time-dependent increase (P < 0.01) in glucose disappearance (93.7 ± 10.0 vs. 69.3 ± 6.3 µmol · kg^-1 · min^-1; P < 0.01) that was evident only during the final hour of study. We conclude that in the presence of hyperglycemia, hyperinsulinemia, and enterally delivered glucose, GLP-1 increases total body but not splanchnic glucose uptake in humans with type 1 diabetes.

Abbreviations: GLP-1, glucagon-like peptide-1(7-36)-amide; SGU, splanchnic glucose uptake; UDP, uridine diphosphate

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