ROLES OF GLYCOGEN AND 5??AMP-ACTIVATED PROTEIN KINASE IN POST-CONTRACTION INSULIN-STIMULATED GLUCOSE TRANSPORT

Abstract

Contractile activity can increase insulin-stimulated glucose transport (GT), i.e., increased insulin sensitivity. Evidence suggests that activation of 5'AMP-activated protein kinase (AMPK) and glycogen depletion can influence insulin sensitivity. PURPOSE The goal of this study was to assess the possible roles of AMPK and glycogen in insulin-stimulated GT after contractile activity. METHODS Previously, we performed a series of 4 experiments, in which only 1 parameter of the contraction protocol was varied for each experiment (i.e., train duration, train rate, pulse frequency, or # of 5 min bouts); 3.5 hr later, we measured insulin-stimulated GT. Male Wistar rats were anesthetized, and one nerve was electrically stimulated to contract. Both epitrochlearis muscles were then incubated in vitro for 3.5 hr before insulin-stimulated GT was measured. The results of these experiments identified a dose response such that there was an apparent threshold, above which there was a significant increase in insulin sensitivity. In the present study, for each contraction parameter, AMPK phosphorylation and glycogen concentration were determined using two contraction protocols: each protocol that was below and above the apparent threshold. Again, one nerve was stimulated to contract, and muscles were frozen immediately after contraction and subsequently used to measure glycogen or AMPK phosphorylation. RESULTS Compared to non-contracting controls, glycogen was reduced and AMPK phosphorylation was increased for each contraction protocol shown to induce increased insulin sensitivity. Furthermore, some of the contraction protocols which did not induce increased insulin sensitivity were also characterized by a significant decrease in glycogen and increase in AMPK phosphorylation vs. non-contracting controls. CONCLUSION Glycogen depletion and AMPK phosphorylation may be necessary, but are not sufficient for the post-contraction increase in insulin-stimulated GT in rat skeletal muscle. Supported by AG-10026