FREE FATTY-ACID AND GLUCOSE-METABOLISM IN HUMAN AGING - EVIDENCE FOR OPERATION OF THE RANDLE CYCLE

Free fatty acid and glucose metabolism in human aging: evidence for op eration of the Randle cycle. Am. J. Physiol. 266 (Endocrinol. Metab. 2 9): E501-E509, 1994. - We assessed insulin effects on plasma free fatt y acid (FFA) and glucose metabolism in seven elderly (71 +/- 2 yr) and in seven younger (21 +/- 1 yr) subjects matched for body weight and b ody mass index but not for percent body fat (32.4 +/- 3.8% in elderly vs. 20.4 +/- 3.5% in young, P < 0.05), by performing sequential euglyc emic clamps at five insulin doses (0.6, 1.5, 3, 6, and 15 pmol.min(-1) .kg(-1)) in combination with indirect calorimetry and [1-C-14]palmitat e plus [3-H-3]glucose infusion. At baseline, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were all increased in the elderly (897 +/- 107 vs. 412 +/- 50 mu mol/l and 11.2 +/- 1.4 v s. 5.14 +/- 0.86, 3.45 +/- 0.65 vs. 1.37 +/- 0.25, and 4.63 +/- 0.72 v s. 3.01 +/- 0.33 mu mol.min(-1).kg(-1) lean body mass, P < 0.05 for al l comparisons), whereas glucose turnover was similar as a result of de creased glucose oxidation (8.2 +/- 1.4 vs. 13 +/- 1.9 mu mol.min(-1).k g(-1) lean body mass, P < 0.05) and increased glucose storage (6.6 +/- 1.4 vs. 1.7 +/- 1.3 mmol.min(-1).kg(-1) lean body mass, P < 0.05). At all insulin infusions, plasma FFA concentration, turnover and oxidati on, and total lipid oxidation were higher in the elderly than in the y ounger group (P < 0.05). However, if normalized per fat mass, all FFA and lipid metabolic fluxes, both in the postabsorptive state and durin g hyperinsulinemia, were comparable in the two groups. Insulin-mediate d inhibition of hepatic glucose production and stimulation of glucose storage were similar in the two groups, but glucose oxidation was lowe r in the elderly than in the young at all insulin concentrations teste d (P < 0.05). Plasma FFA turnover rate and total lipid oxidation were negatively correlated with whole body glucose uptake and oxidation in the two groups (P < 0.05-0.01). Thus, in human aging, abnormalities in insulin regulation of FFA/lipid metabolism may be secondary to increa sed fat mass and substrate competition between fat and glucose and may play a role in determining a reduction in insulin-mediated glucose ox idation.