Abstract
ObjectiveTo assess if glucagon‐like peptide (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) have a direct effect on glucose metabolism independent of their effect on the endocrine pancreas.MethodsFive healthy males (22+/−1 years, BMI 21+/−1) with normal glucose metabolism (fasting glucose = 5.0+/−0.1 mM, HbA1c = 5.2+/−0.1%) were studied using the pancreatic clamp technique (100 ng/kg/min somatostatin infusion with basal replacement of insulin, glucagon and growth hormone) in 3 different trials (GLP‐1 [0.5 pmol/kg/min], GIP [1.5 pmol/kg/min] or saline infusion). A 2‐step clamp was performed at euglycemic (90 min) and hyperglycemic (90 min; euglycemic + 5.4 mM) levels. Peripheral blood flow and vascular function (forearm flow‐mediated dilation; FMD) were determined by ultrasound Doppler.ResultsInsulin was maintained at basal levels during euglycemia in all 3 trials, with equal decreases in C‐peptide levels. During hyperglycemia, insulin and C‐peptide levels increased in all trials (P<0.05). Glucose infusion rates were higher during euglycemia in the GLP‐1 trial as compared to the saline trial (P<0.05), also when adjusted for insulin values (P=0.10). Peripheral blood flow and vascular function did not differ between trials.ConclusionThese data suggest a direct insulin/glucagon‐independent effect of GLP‐1 on glucose metabolism during euglycemia.
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