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 tissues, we measured the amount of PDHC in the active form in heart, diaphragm, red quadriceps, white adipose tissue (WAT), and brown adipose tissue (BAT) of rats exposed to five different circulating insulin concentrations under euglycemic clamp conditions. PDHC was measured in mitochondrial extracts of tissues rapidly dissected from rats in the starved 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 concentration increased the PDHC activity in all tissues, but the magnitude of this activation was different in different tissues (heart: 3.5-fold; diaphragm: 2.5-fold; red quadriceps: 1.8-fold; WAT: 3.4-fold; and BAT: 10.5-fold). Calculation of the half-maximal effective dose (ED50) for the activation of PDHC produced values that were similar in all tissues (heart: 112 pM; diaphragm: 108 pM; red quadriceps: 146 pM; WAT: 120 pM; and BAT: 118 pM). The insulin sensitivity of PDHC in these tissues correlated particularly well with the ED50 for the insulin effect of decreasing circulating nonesterified fatty acids (NEFA; 122 pM). The differences in the magnitude of the effect of increasing insulin on PDHC activity implies a tissue difference in the requirment for an increased capacity for glucose oxidation after insulin stimulation. The correlation between the insulin sensitivity of NEFA availability, glucose turnover, and PDHC activity is consistent with the concept of the operation of a glucose-fatty cycle in the control of glucose oxidation in individual tissues of the rat.