Incretin hormones (GLP-1 and GIP) have insulin secretory effects on the pancreas that are glucose dependent. Extrapancreatic effects of incretin hormones are reported, however the glucose dependency of these effects have not been examined. In type 2 diabetes, pancreatic endocrine function and incretin metabolism are impaired. The investigators hypothesize that extrapancreatic effects of incretin hormones are glucose depedent and dysregulated in subjects with type 2 diabetes. Healthy control subjects and type 2 diabetics will undergo pancreatic clamps. In brief, somatostatin will be infused to inhibit pancreatic endocrine function and basal levels of insulin, glucagon, and growth hormone will be replace via infusion. Metabolic flux will be studied during euglycemic and hyperglycemic stages of the pancreatic clamp. Each subject will undergo 3 trials involving the co-infusion of either saline(Control Trial), GLP-1, or GIP. Glucose metabolism will be assessed using 13C-glucose stable isotope methodology combined with indirect calorimetry and expired breath isotope ratio analysis. Blood flow and flow-mediated dilation will be measured using ultrasound Doppler. Skeletal muscle and abdominal adipose biopsies will be taken to examine intracellular signalling.
Study Type
OBSERVATIONAL
Enrollment
20
Rigshospitalet
Copenhagen, Denmark
Glucose turnover
Rates of appearance and disappearance (g/min) will be measured by examining \[6,6-2H2\]glucose enrichment in plasma.
Time frame: 0, 1, 2, 3, 4 hours
Blood flow and flow-mediated dilation
Time frame: 0, 1, 2, 3, 4 hours
Palmitate turnover and oxidation
Rates of appearance and disappearance (g/min) will be measured by examining \[U13C\]palmitate enrichment in plasma. Rate of oxidation (g/min) will also be measured by examining 13C incorporation into CO2 in expired breath.
Time frame: 0, 1, 2, 3, 4 hours
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