Forearm insulin- 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 micrograms/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 less than .05), and an acute increase in FFA levels decreased the MNIMGU by 26% (P less than .05). MIMGU was significantly increased by 103% after acipimox administration (P less than .05) and was decreased by 65% during intralipid infusion (P less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)