Lactate turnover and gluconeogenesis in obesity. Effect of phenformin.

Abstract

The effect of phenformin on the rates of lactate and glucose turnover, interconversion, and oxidation was determined in five obese subjects with normal glucose tolerance. L (+) lactate-U (50 μc.) and glucose 1-C-14 were administered over four-hour periods on consecutive days by a primed infusion technic. One hundred to 150 mg. of phenformin was administered daily, and the turnover studies were repeated on the sixth and seventh days of therapy. Phenformin increased glucose turnover by 10 per cent, from 95.6 ± 4.4 to 106.2 ± 4.7 (mean ± S.E.M.) mg,/kg./ hr. and glucose recycling by 100 per cent, from 8.7 ± 1,4 to 19.3 ± 1.3 mg./kg./hr. In contrast, the changes in glucose oxidation were inconsistent, decreasing in three subjects and increasing in two. As expected, the blood glucose concentration and glucose pool were unchanged during treatment with phenformin. Lactate turnover increased 30 per cent, from 63.5 ± 3.5 to 82.8 ± 5.7 mg./kg./hr., and lactate derived from glucose (glucose conversion to lactate) increased 25 per cent, from 57.9 ± 5.5 to 71.8 ± 6.9 mg./kg./hr. Lactate conversion to glucose increased in all subjects by a mean of 13.1 ± 1.2 mg./kg./hr., from 15.2 ± 1.2 to 28.2 ± 1.8 mg./kg./hr. The increase in lactate conversion to glucose was almost identical to the increase in glucose turnover and glucose conversion to lactate. During therapy with phenformin, 34.1 ±1.2 per cent of the lactate turnover was converted to glucose in contrast to 22.1 ± 1.3 per cent before therapy. These results demonstrate that phenformin enhances the interconversion of glucose and lactate in subjects in whom it exerts no hypoglycemie effect.