Pretransplant aerobic exercise improves glycemic outcomes after marginal islet mass transplantation in rats.

Abstract

Pancreatic islet transplantation (ITx) improves glycemic management and prevents severe hypoglycemia in select individuals with type 1 diabetes (T1D). However, insulin independence cannot be guaranteed due to transplant and recipient-specific factors, limiting broad application. Exercise improves insulin sensitivity, reduces chronic inflammation, increases insulin-independent glucose uptake, and can decrease the risk of surgery-related complications. Therefore, we examined the utility of pretransplant exercise in the context of ITx on metabolic and immune outcomes. Streptozotocin (STZ)-induced diabetic rats performed voluntary, 1-h wheel-running exercise in an overnight-fasted state on three nonconsecutive days weekly for 4 wk preceding transplantation. Exercised (RUN, n = 7) and sedentary (SIT, n = 6) rats underwent marginal syngeneic ITx. Graft efficacy was compared with nonfasted blood glucose readings and a 4-wk intraperitoneal glucose challenge. At 4 wk posttransplant, 100% (7/7) of RUN rats became euglycemic compared with 66% (4/6) in the SIT condition (P < 0.05). RUN recipients demonstrated superior nonfasting blood glucose and weight gain (P < 0.05) and comparable glucose tolerance to naïve rats, whereas SIT rats had inferior clearance (P < 0.05), despite comparable proportions of insulin and glucagon graft-positive cells. Reduction in RUN adipose tissue macrophages suggests lower inflammation levels alongside greater insulin sensitivity based on the quantitative insulin-sensitivity check index (QUICKI) (P < 0.01). Moreover, the soleus muscle of RUN recipients had lower levels of pyruvate dehydrogenase phosphorylation at serine 232 (P < 0.05), and increased levels of phosphorylated glycogen synthase kinase (P < 0.05), suggestive of increased carbohydrate oxidation and insulin signaling, respectively. Altogether, we demonstrate that pretransplant exercise may enhance glycemic outcomes in ITx due to lower inflammation levels and increased carbohydrate oxidation.NEW & NOTEWORTHY To our knowledge, there have yet to be any formal investigations into the role of prehabilitation exercise in ITx. Our exciting preliminary work highlights a noninvasive and feasible approach that may improve the outcomes of this functionally curative procedure. Our findings presented support additional investigation into prehabilitation in ITx, which can encompass a wide array of exercise regimens.