Control of Insulin Secretion and Glucose Homeostasis in Exercising Diabetic Rats with Intrasplenic or Kidney Subcapsular Islet Grafts

Abstract

This study was designed 1) to investigate mechanisms of insulin secretion during exercise after transplantation of islets in the spleen and under the kidney capsule, and 2) to compare these organs as transplantation site regarding an adequate portal or systemic delivery of insulin and glucose homeostasis during exercise. Diabetic rats were provided with 5 μL isogenic islet tissue in the spleen or under the kidney capsule, which results in normoglycemia, and were submitted to a swimming test Portal plasma insulin levels were higher than simultaneously sampled systemic insulin levels in the control and in the intrasplenic islet grafted group, but not in the kidney subcapsular islet-grafted group. Plasma portal and systemic insulin levels decreased, and glucose levels increased during exercise in all groups. The exercise-induced increase in levels of catecholamines was larger in systemic than in portal plasma, suggesting catecholamine extraction by the lungs or intestines. The experiments were repeated after removing of adrenal medulla, resulting in nondetectable or very low plasma adrenaline levels. Despite these low adrenaline levels, insulin levels decreased during exercise. The results indicate that 1) the exercise-induced reduction of insulin secretion is not mediated by circulating adrenaline, but is probably under control of the sympathetic nervous system, which could be the result of reinnervation of the transplanted islets. 2) Although a portal-systemic insulin gradient was absent in rats with kidney subcapsular islet grafts, the absence of a difference in glucose homeostasis during exercise between the sites revealed that all investigated sites are preferential to transplant islets.