Direct effect of GLP-1 infusion on endogenous glucose production in humans

作者：Seghieri M; Rebelos E; Gastaldelli A; Astiarraga B D; Casolaro A; Barsotti E; Pocai A; Nauck M; Muscelli E; Ferrannini E^*

来源：Diabetologia, 2013, 56(1): 156-161.

DOI：10.1007/s00125-012-2738-3

• Endogenous glucose production
• GLP-1
• Liver glucose output
• Pancreatic clamp

Glucagon-like peptide-1 (GLP-1) lowers glucose levels by potentiating glucose-induced insulin secretion and inhibiting glucagon release. The question of whether GLP-1 exerts direct effects on the liver, independently of the hormonal changes, is controversial. We tested whether an exogenous GLP-1 infusion, designed to achieve physiological postprandial levels, directly affects endogenous glucose production (EGP) under conditions mimicking the fasting state in diabetes. %26lt;br%26gt;In 14 healthy volunteers, we applied the pancreatic clamp technique, whereby plasma insulin and glucagon levels are clamped using somatostatin and hormone replacement. The clamp was applied in paired, 4 h experiments, during which saline (control) or GLP-1(7-37)amide (0.4 pmol min(-1) kg(-1)) was infused. %26lt;br%26gt;During the control study, plasma insulin and glucagon were maintained at basal levels and plasma C-peptide was suppressed, such that plasma glucose rose to a plateau of similar to 10.5 mmol/l and tracer-determined EGP increased by similar to 60%. During GLP-1 infusion at matched plasma glucose levels, the rise of EGP from baseline was fully prevented. Lipolysis (as indexed by NEFA concentrations and tracer-determined glycerol rate of appearance) and substrate utilisation (by indirect calorimetry) were similar between control and GLP-1 infusion. %26lt;br%26gt;GLP-1 inhibits EGP under conditions where plasma insulin and glucagon are not allowed to change and glucose concentrations are matched, indicating either a direct effect on hepatocytes or neurally mediated inhibition.

• 出版日期2013-1