Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for the abnormal response to insulin. Likewise, the investigators do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators will measure muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates under both saline control (high overnight FFA) and after an overnight infusion of intravenous niacin (lower/normal FFA) to provide the first integrated examination of the interaction between FFA and muscle insulin action from the whole body to the cellular/molecular level. By identifying which steps in the insulin signaling pathway are most affected, the investigators will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance. Hypothesis 1: Greater trafficking of plasma FFA into intramyocellular DG will impair proximal insulin signaling and reduce muscle glucose uptake. Hypothesis 2: Lowering FFA in UBO and T2DM by using an intravenous infusion of niacin will alter trafficking of plasma FFA into intramyocellular ceramides in a way that will improve insulin signaling and increase muscle glucose uptake. Hypothesis 3: Lowering FFA in UBO and T2DM by using an intravenous infusion of niacin will alter trafficking of plasma FFA into intramyocellular DG in a way that will improve insulin signaling and increase muscle glucose uptake.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Glucose Infusion Rate
Glucose infusion rates will be measured in upper body obese and type 2 diabetic volunteers using hyperinsulinemic, euglycemic clamp under saline control conditions and during an intravenous infusion of niacin. The hyperinsulinemic-euglycemic clamp is a method used to measure insulin sensitivity. Plasma insulin concentration is acutely raised and maintained at \~40-80 μU/ml (microunits per milliliter) by continuous insulin infusion. During the clamp, the plasma glucose concentration was held constant at normal blood sugar level. The glucose infusion rate over the last hour of the insulin infusion is the net effect of insulin on whole-body glucose metabolism. This rate serves as a measure of tissue insulin sensitivity. The hyperinsulinemic-euglycemic clamp assesses how sensitive your tissues are to insulin.
Time frame: 18 hours
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.