Exercise training attenuates cerebral ischemic hyperglycemia by improving hepatic insulin signaling and β-cell survival

AimsPreventing hyperglycemia after acute stroke attenuates complications of cerebral ischemia and reduces the risk of mortality. We investigated whether regular exercise prevents neuronal cell death and post-stroke hyperglycemia in gerbils after cerebral ischemia.Main methodsCerebral ischemia was induced by carotid artery occlusion for 8 min. The gerbils that underwent ischemic or sham operations were randomly subdivided into exercise (ran on inclined treadmill at 20 m/min for 30 min 5 days per week for 1 week prior to surgery) or non-exercise groups. Gerbils were fed a 40% fat diet and after 28 days, glucose metabolism, serum cytokine levels and cognitive function was measured.Key findingsArtery occlusion resulted in a 64% reduction in hippocampal CA1 neurons in comparison to the sham gerbils, and caused decreased neuronal mass and impaired cognitive function. Exercise partially prevented neuronal death and improved ischemia-induced glucose intolerance. Ischemia decreased hepatic insulin signaling and exacerbated insulin resistance whereas exercise prevented the disturbance. Insulin secretion was lower in ischemic gerbils than sham gerbils, due to lowered pancreatic β-cell mass caused by increased β-cell apoptosis and decreased β-cell proliferation, which were also prevented by exercise. Increase of apoptosis was associated with elevated caspase-3 activity, consistent with increased serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels.SignificanceHippocampal neuronal cell death induces hyperglycemia due to attenuated hepatic insulin signaling and decreased β-cell mass by increased β-cell apoptosis through increased TNF-α and IL-1β levels. Exercise partially prevents this phenomenon suggesting that exercise training may provide neuroprotective benefits from cerebral ischemic hyperglycemia.