Lack of effect of hyperglycemia on lipolysis in humans

Controversy exists regarding whether plasma glucose concentrations are independently involved in the regulation of adipose tissue lipolysis. In the present study, six subjects with insulin-dependent diabetes and six nondiabetic volunteers were studied during infusion of somatostatin, growth hormone, and insulin at rates designed to maintain basal rates of lipolysis, which was traced using a constant infusion of [1-¹⁴C]palmitate. A euglycemic (~ 5 mmol/l) clamp was performed for 3 h, followed by 3 h of hyperglycemia (~ 9 and ~ 11 mmol/l in nondiabetic and diabetic subjects, respectively). Ten nondiabetic subjects were studied during 6 h of euglycemia to exclude time-dependent changes in lipolysis. The results showed that palmitate concentrations did not change between euglycemia and hyperglycemia in either group [118 ± 10 vs. 132 ± 14 μmol/l and 145 ± 21 vs. 134 ± 15 μmol/l in nondiabetic and diabetic subjects, respectively; both P = not significant (NS)]. Similarly, palmitate rate of appearance (R(a)) did not change during hyperglycemia (1.0 ± 0.1 and 1.7 ± 0.4 μmol · kg^-1 · min^-1 in nondiabetic and diabetic subjects, respectively) compared with euglycemia (1.0 ± 0.1 and 1.6 ± 0.4 μmol · kg^-1 · min^-1 in nondiabetic and diabetic subjects, respectively; P = NS). Palmitate concentrations and R(a) did not change during 6 h of euglycemia in nondiabetic volunteers. Thus hyperglycemia per se has no effect on free fatty acid turnover. Changes in lipolysis that occur coincident with hyperglycemia are probably due to changes in other circulating substrates or hormones known to affect lipolysis.