We used stable
isotope-labeled
glucose and
palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron emission tomography of muscles and adipose tissue after [
18F]fluorodeoxyglucose and [15O]water
injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that 1) increased
glucose uptake in SAT is responsible for high
insulin-stimulated whole-body
glucose uptake in people with
obesity who are
insulin sensitive and 2) putative SAT factors thought to cause
insulin resistance are present in people with
obesity who are
insulin resistant but not in those who are
insulin sensitive. We found that high
insulin-stimulated whole-body
glucose uptake in
insulin-sensitive participants with
obesity was not due to channeling of
glucose into SAT but, rather, was due to high
insulin-stimulated muscle
glucose uptake. Furthermore,
insulin-stimulated muscle
glucose uptake was not different between
insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT
inflammation,
fatty acid appearance in plasma in relation to fat-free mass, and plasma
fatty acid concentration were higher in the
insulin-sensitive obese than in lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT
inflammation between
insulin-resistant and
insulin-sensitive obese participants. Plasma
fatty acid concentration was also not different between
insulin-sensitive and
insulin-resistant obese participants, even though SAT was resistant to the inhibitory effect of
insulin on lipolysis in the
insulin-resistant obese group. These data suggest that several putative SAT factors commonly implicated in causing
insulin resistance are normal consequences of SAT expansion unrelated to
insulin resistance.