IN-VIVO INSULIN SENSITIVITY OF THE PYRUVATE-DEHYDROGENASE COMPLEX IN TISSUES OF THE RAT

Activity of the insulin-activated pyruvate dehydrogenase complex (PDHC ) is necessary for the complete oxidation of glucose to carbon dioxide or the conversion of glucose to fatty acids in lipogenic tissues. To determine the in vivo insulin sensitivity of PDHC activity in rat tiss ues, we measured the amount of PDHC in the active form in heart, diaph ragm, red quadriceps, white adipose tissue (WAT), and brown adipose ti ssue (BAT) of rats exposed to five different circulating insulin conce ntrations under euglycemic clamp conditions. PDHC was measured in mito chondrial extracts of tissues rapidly dissected from rats in the starv ed state or after euglycemic clamp (4 mM) at insulin infusion rates of 0, 0.125, 0.25, and 2.0 U.kg-1.h-1. Increasing the insulin concentrat ion increased the PDHC activity in all tissues, but the magnitude of t his activation was different in different tissues (heart: 3.5-fold; di aphragm: 2.5-fold; red quadriceps: 1.8-fold; WAT: 3.4-fold; and BAT: 1 0.5-fold). Calculation of the half-maximal effective dose (ED50) for t he activation of PDHC produced values that were similar in all tissues (heart: 112 pM; diaphragm: 108 pM; red quadriceps: 146 pM; WAT: 120 p M; and BAT: 118 pM). The insulin sensitivity of PDHC in these tissues correlated particularly well with the ED50 for the insulin effect of d ecreasing circulating nonesterified fatty acids (NEFA; 122 pM). The di fferences in the magnitude of the effect of increasing insulin on PDHC activity implies a tissue difference in the requirment for an increas ed capacity for glucose oxidation after insulin stimulation. The corre lation between the insulin sensitivity of NEFA availability, glucose t urnover, and PDHC activity is consistent with the concept of the opera tion of a glucose-fatty cycle in the control of glucose oxidation in i ndividual tissues of the rat.