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Updated: Apr 11, 2026
A Method for Murine Islet Isolation and Subcapsular Kidney Transplantation
Published on: April 13, 2011
Pretransplant aerobic exercise improves glycemic outcomes after marginal islet mass transplantation in rats
Jordan M Wong1, Seyed Amirhossein Tabatabaei Dakhili2, Purushothaman Kuppan1
1Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
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.
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.
