LOW-CARBOHYDRATE DIET ALTERS INTRACELLULAR GLUCOSE-METABOLISM BUT NOT OVERALL GLUCOSE DISPOSAL IN EXERCISE-TRAINED SUBJECTS

Dietary composition has been strongly implicated as an important determinant of in vivo insulin sensitivity. However, the metabolic alterations associated with extreme changes in diet have not been well described. We compared glucose metabolism after a standard diet ([STD] 35% fat, 51% carbohydrate, and 14% protein) with the effects of a 3-week adaptation to a low-carbohydrate, high-fat diet ([LCD] 75% fat, 8% carbohydrate, and 17% protein). Ten healthy men were studied using the euglycemic clamp technique, indirect calorimetry, and percutaneous vastus lateralis muscle biopsies for analysis of glycogen synthase (GS) and pyruvate dehydrogenase (PDH) activities in the basal and insulin-stimulated states. Insulin-stimulated glucose disposal was unchanged (STD 46.1 +/- 4.3 v LCD 46.0 +/- 4.3 mu mol/kg . min, P = NS), but marked alterations in the routes of glucose disposal were noted. Insulin-stimulated glucose oxidation (G(ox)) was markedly reduced following LCD (STD 18.6 +/- 1.9 v LCD 8.23 +/- 1.9 pmol/kg min, P=.0001), and nonoxidative glucose metabolism (G(nox)) was enhanced by LCD (STD 24.9 +/- 0.9 v LCD 38.9 +/- 4.3 mu mol/kg . min, P=.03). Following LCD, both the total and active forms of PDH (PDHt and PDHa) were significantly depressed. After LCD, GS activities (FV0.1, %I, and A(0.5)) were unaffected in the basal state, but were greater than for STD (P=.004) after insulin stimulation. The apparent increase in the sensitivity of GS to activation by insulin following LCD correlated strongly with maximal O-2 consumption ([Vo(2)max] r=.97, P=.001), suggesting that physical conditioning interacted with the metabolic impact of LCD. In summary, LCD did not induce changes in net glucose disposal. However, LCD decreased insulin-stimulated G(ox), with a correspondingly diminished activity of PDH, the rate limiting enzyme for G(ox). There was a reciprocal increase in insulin-stimulated G(nox) concomitant with increased activation of GS, which was consistent with increased potential for glycogen synthesis.