Insulin Stimulated Lactate Production

Abstract

It has been shown that Type 2 diabetic patients who undergo Roux-en-Y Gastric Bypass surgery (RYGB) show a decrease in muscle lactate production, liver glucose production and pancreatic insulin secretion. To explain these changes, it is hypothesized that gastric bypass surgery “removes” a block at pyruvate oxidation in both muscle and liver. A block at pyruvate oxidation prior to RYGB would cause pyruvate to accumulate in the muscle and its only pathway for disposal would be through export as lactate. After RYGB, pyruvate dehydrogenase would be activated, allowing pyruvate to be oxidized. Thus, lactate would not be exported from the muscle, reducing the availability of this gluconeogenic substrate. Elevated lactate levels drive glucose production. The rapid remission of diabetes after RYGB is accompanied by a reduction in blood lactate concentrations and therefore a reduction in fasting glucose concentration.

This study was done to compare glucose and lactate levels in subjects 1-3 years post RYGB to age- and BMI-matched control subjects. Our hypothesis was that there will be no significant differences in glucose and lactate levels in subjects post-RYGB and control subjects, suggesting that RYGB causes these levels to return to normal. Each subject underwent an intravenous glucose tolerance test and blood samples were taken at baseline and 29 additional time points over the course of three hours. Each blood sample was analyzed for glucose and lactate values and the results between the two groups were compared.

Our results show that on average, lactate values in RYGB patients are lower than their age- and BMI-matched controls, suggesting that the surgery induces a lasting change in skeletal muscle metabolism, which enables the oxidation of glucose.