Does sex or exercise modality influence post-exercise glucose handling or insulin sensitivity?

Abstract

Exercise has long been recognized for its beneficial effects on glucose handling in both insulin sensitive and insulin resistant populations. However, there is conflicting evidence in regards to the best type and duration of exercise to elicit the greatest benefit on glucose metabolism. Additionally, biological sex is known to influence the metabolic response to both acute and chronic bouts of exercise. Therefore, the purpose of this thesis was to examine the acute effects of three different modes of exercise on post-exercise glucose handling in young, healthy males and females. In Study 1, twenty-four recreationally active males and females (n=12/sex) completed an acute bout of high intensity interval exercise (HIIE, 10x1min at 90% HRmax), to evaluate whether sex influenced the physiological effects of HIIE on post-exercise glycemic control during an oral glucose tolerance test (OGTT). We also examined whether sex differences in post-exercise glycemic control were related to sex differences in muscle metabolism and/or insulin signaling proteins. HIIE increased post-exercise insulin sensitivity in both sexes characterized by the Matsuda and homeostatic model assessment for insulin resistance (HOMA-IR) indices. We also found that HIIE lowered insulin concentration during the OGTT compared to the control OGTT. When normalized for glucose dose relative to lean body mass, glucose area under the curve (AUC) was lower in females than males. While we did not find any difference in total insulin signaling protein content, muscle glycogen utilization or AMPK activation during exercise between the sexes, we found that TBC1D1 Ser237 phosphorylation increased in males, but not females, post-exercise. Overall, these findings indicate that when the glucose dose is normalized for differences in body composition glycemic handling is better in females and that an acute bout of HIIE improves insulin sensitivity equally in healthy males and females. In study 2, we sought to examine the effect of sex on markers of oxidative stress and inflammation following an acute bout of HIIE and during an OGTT. Twenty-four (12/sex) males and females matched for aerobic fitness (V̇O₂peak relative to lean body mass) had muscle biopsies taken at rest and following an acute bout of high-intensity interval exercise (HIIE, 10x1min at 90% HRmax) and blood taken at rest, post exercise, 90 minutes post exercise (immediately prior to an OGTT) and at 60 min during the OGTT. Muscle biopsies were analyzed for markers of oxidative stress/oxidant generation (NOX2, 4HNE, p38 MAPK) and antioxidant status (TRX1, glutathione reductase, GPX1) and blood samples were analyzed for inflammatory markers (IL-6 and TNFα). Following exercise there was an increase in plasma concentrations of IL-6 and TNFα, with IL-6 continuing to increase during the OGTT, with no differences between the sexes at rest or following exercise. We did not see any effect of sex on antioxidant or oxidative stress status; however, we did find that females had higher p38 MAPK phosphorylation at rest compared to males. Overall, these findings suggest that antioxidant status, ROS production and inflammation do not differ between males and females at rest, following an acute bout of HIIE or during a post-exercise glucose challenge. In study 3, twenty-four (n=12/sex) participants completed acute bouts of MIC exercise (30mins at 65% V̇O₂peak) and LLHR (3 circuits, 6 exercises/circuit, 25-35 repetitions/exercise/ circuit) to compare the acute effects of each of these exercise bouts on post-exercise glycemic control and insulin sensitivity. Blood glucose concentrations were lower during a post-exercise OGTT following LLHR RE compared to MIC exercise in males and females. Glucose AUC was also lower in both sexes. In males and females phosphorylated ACC Ser79 increased following MIC exercise only, with no changes following LLHR RE. These findings suggest that LLHR RE is a feasible exercise modality to improve post-exercise glycemic control in males and females. In conclusion we found that LLHR RE decreased blood glucose concentrations to a greater extent than MIC exercise. Additionally, we found that acute HIIE was able to improve post-exercise IS in both sexes. While absolutely glucose concentrations did not differ between males and females, we found that once blood glucose concentrations were normalized to body weight and lean body mass, females had lower glucose concentrations compared to males. The collective results from this thesis indicate that there are some slight differences between the sexes in the metabolic response to acute exercise that may influence pathways responsible for glucose uptake. Overall, the work done in this thesis provides necessary proof of concept for future sex comparative research done in the area of exercise and glucose handling in individuals with insulin resistance.