FOREARM INSULIN-MEDIATED AND NON-INSULIN-MEDIATED GLUCOSE-UPTAKE AND MUSCLE METABOLISM IN MAN - ROLE OF FREE FATTY-ACIDS AND BLOOD-GLUCOSE LEVELS

Muscle can utilize glucose by two different mechanisms, one non-insulin-mediated and the other insulin-mediated. The aim of this study was to investigate and to quantify the influence of high and low free fatty acids (FFA) levels on muscle non-insulin-mediated glucose uptake (MNIMGU) and muscle insulin-mediated glucose uptake (MIMGU) and on muscle metabolism during euglycemia and hyperglycemia. Six healthy volunteers were submitted, in a random order, to a 2-hour euglycemic clamp (EC) followed by a 2-hour hyperglycemic (11 mmol/L) clamp (HC) under five different conditions: (1) somatostatin infusion (SRIF, 500 μg/h); (2) SRIF infusion preceded by a nicotinic acid analogue (acipimox, 250 mg orally), (3) SRIF plus insulin infusion; (4) SRIF plus insulin plus intralipid infusion; and (5) SRIF plus insulin infusion plus acipimox. In the postabsorptive state MNIMGU represented 71% of the total muscle glucose uptake (MGU) and during the EC a sharp reduction of FFA levels increased the MNIMGU by 10% (P < .05), and an acute increase in FFA levels decreased the MNIMGU by 26% (P < .05). MIMGU was significantly increased by 103% after acipimox administration (P < .05) and was decreased by 65% during intralipid infusion (P < .05). During HC, MNIMGU was not significantly influenced by low or high FFA levels, and MIMGU was not affected by a sharp lowering of FFA levels, but was significantly decreased (85%) during intralipid infusion. There was no significant difference in the lactate, pyruvate, and alanine balance across the forearm during EC and HC. In conclusion, (1) an acute reduction of FFA levels produces a significant increase of MNIMGU and of MIMGU only in euglycemia; (2) an increase of FFA levels reduces the MIMGU both in euglycemia and in hyperglycemia; and (3) FFA, at least under these circumstances, do not modify the muscle balance of the main gluconeogenic precursors. © 1991.