Lactate Turnover and Gluconeogenesis in Normal and Obese Humans: Effect of Starvation

Abstract

Turnover rates of lactate and glucose were determined in normal, obese, and fasted obese human subjects. L—(+) lactate-U-C-14 (50μc.) and glucose-l-C-14 (50 μc.) were administered over a four-hour period on consecutive days by a primed-infusion technic. Lactate and glucose interconversion rates were calculated from precursor-product specific activity ratios obtained during the infusion period and the rates of lactate and glucose turnover. Glucose turnover, oxidation, recycling, and conversion to lactate, when expressed on a mg./kg./hr. basis, were significantly less in obese subjects than in normals; however, when expressed as a percentage of the turnover, no significant differences were observed. Glucose oxidation represented 14 per cent; recycling, 10 per cent; and conversion to lactate, 66 per cent of the glucose turnover rate. Approximately 15 per cent of the glucose turnover was derived from lactate. In contrast, there were no significant quantitative or qualitative differences in the metabolism of lactate by normal or obese subjects. Lactate oxidation represented 11 per cent and lactate conversion to glucose 21 per cent of the lactate turnover rate. During starvation, there was a 30 per cent reduction in glucose pool size, turnover, and oxidation. Blood lactate concentrations and lactate turnover were unchanged despite decreased conversion of glucose to lactate. The conversion of lactate to glucose increased from 14 ± 2 to 21 ± 2 mg./kg./hr. and represented 36 per cent of the lactate turnover. The fraction of the glucose turnover derived from lactate increased two-fold, from 17 to 38 per cent. These results are in general agreement with those obtained in animals and are the first quantitative estimates of lactate-glucose interconversion rates in man. The combination of decreased glucose conversion to lactate and increased lactate conversion to glucose in the presence of an unchanged blood lactate concentration and turnover requires that there be increased synthesis of lactate from sources other than glucose. In addition, increased conversion of lactate to glucose at unchanged blood concentrations indicates enhanced extraction of lactate during starvation.