Human Models of Selective Insulin Resistance: Pancreatic Clamp

Insulin infusion rate (IIR) will be determined either to maintain fasting serum insulin levels (MH protocol) or to reduce fasting serum insulin levels by approximately 50% toward euinsulinemia (RE protocol).

Octreotide will be infused at 30 ng/kg/min to suppress endogenous insulin, glucagon, and growth hormone secretion. Co-administered with glucagon and rhGH.

Glucagon will be replaced at a constant rate of up to 0.65 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and rhGH.

Recombinant human growth hormone (rhGH) will be replaced at a constant rate of up to 3 ng/kg/min to maintain baseline counterregulatory response. Co-administered with octreotide and glucagon.

20% D-glucose (aq) (D20W) will be administered to counteract hypoglycemia or strongly downward blood glucose trends, as needed.

Stable isotope tracer administered to calculate glucose kinetics during pancreatic clamp.

Stable isotope tracer administered to calculate de novo lipogenesis during pancreatic clamp.

"Nutritional supplement will be administered to provide standardized mixed meals prior to the pancreatic clamp."

Energy bar snack will be administered the evening before the pancreatic clamp.

Syringe pump used for highly precise administration of insulin, octreotide/glucagon/rhGH, and D20W (as needed) even at low infusion rates.

Glucose oxidase analyzer used to detect plasma glucose levels at the point of care. YSI have been the gold standard in clamp studies for many years. Two machines will run in parallel to ensure accuracy of results.