LACTATE INFUSION TO NORMAL RATS DURING HYPERGLYCEMIA ENHANCES IN-VIVOMUSCLE GLYCOGEN-SYNTHESIS

Both hyperglycemia and hyperinsulinemia stimulate whole body and muscl e glucose disposal. To define the impact of increased lactate concentr ation (4-5 mM) on muscle glucose disposal during hyperglycemia, we stu died anesthetized normal rats infused with either sodium lactate or so dium bicarbonate as control. Animals were studied under hyperglycemic clamp (13 mM) using [3-H-3]glucose (study I) and 2-deoxy-[1-H-3]glucos e (study 2) to assess glucose rate of disappearance (R-d), glycolytic flux (GF), glycogen synthesis, and glucose utilization index by differ ent tissues. Moreover, in study 3, the effect of lactate on the patter n of plasma insulin response to hyperglycemia was evaluated. In study 1, lactate infusion resulted in an increased R-d (38.7 +/- 1.7 vs. 32. 3 +/- 1.3 mg.min(-1).kg(-1); P < 0.01), which was explained by an enha nced rate of glycogen synthesis (23.0 +/- 1.7 vs. 14.7 +/- 1.2 mg. min (-1).kg(-1); P < 0.001), whereas GF was unchanged. In study 2, lactate -infused animals showed an increased 8-deoxyglucose disposal and a sti mulated glycogen synthase activity as well as an increased glycogen ac cumulation at the end of the study in several skeletal muscles. In stu dy 3, lactate did not induce any change in either early or late insuli n response to hyperglycemia. In conclusion, our results show that musc le glycogen deposition may be enhanced by elevated lactate levels unde r hyperglycemic conditions and support a role for lactate in the regul ation of glucose homeostasis.