Overexpression of Insulin Degrading Enzyme could Greatly Contribute to Insulin Down-regulation Induced by Short-Term Swimming Exercise

Abstract

Exercise training is highly correlated with the reduced glucose-stimulated insulin secretion (GSIS), although it enhanced insulin sensitivity, glucose uptake and glucose transporter expression to reduce severity of diabetic symptoms. This study investigated the impact of short-term swimming exercise on insulin regulation in the Goto-Kakizaki (GK) rat as a non-obese model of non-insulin-dependent diabetes mellitus. Wistar (W/S) and GK rats were trained 2 hours daily with the swimming exercise for 4 weeks, and then the changes in the metabolism of insulin and glucose were assessed. Body weight was markedly decreased in the exercised GK rats compare to their non-exercised counterpart, while W/S rats did not show any exercise-related changes. Glucose concentration was not changed by exercise, although impaired glucose tolerance was improved in GK rats 120 min after glucose injection. However, insulin concentration was decreased by swimming exercise as in the decrease of GSIS after running exercise. To identify the other cause for exercise-induced insulin down-regulation, the changes in the levels of key factors involved in insulin production (C-peptide) and clearance (insulin-degrading enzyme; IDE) were measured in W/S and GK rats. The C-peptide level was maintained while IDE expression increased markedly. Therefore, these results showed that insulin down-regulation induced by short-term swimming exercise likely attributes to enhanced insulin clearance via IDE over-expression than by altered insulin production.

Keywords: C-peptide; Exercise; glucose; insulin; insulin-degrading enzyme.

Figure 1

Scheme of short-term swimming exercise during 3 weeks. A. In the adaptation phase, the swimming time was extended by 10 min every day until reaching 60 min after 6 days. B. In the training phase, all animals were trained for 2 h per day. After swimming exercise, the wet body of rat was rapidly dried with a Kimtowel to maintain body temperature.

Figure 2

Effect of short-term swimming exercise on body weight. Six rats per group were used to measure body weights. The data represents the mean±SD from triplicates. ^*P<0.05; significant difference between W/S and GK rats. ^**P<0.05; significant difference between non-exercise group and exercise group in each rat type.

Figure 3

Post-prandial intraperitoneal glucose tolerance response in W/S (A) and GK (B) rats. Glucose was intraperitoneally injected (1.5 g/kg body weight) and blood glucose was determined at indicated intervals. Four or five rats per group were assayed in the IPGT test. The data represents the mean±SD from triplicates. ^*P<0.05; significant difference between W/S and GK rats.

Figure 4

Effect of short-term swimming exercise on serum insulin concentration. Serum was harvested from the blood sample collected from the abdominal veins of W/S and GK rats. The insulin level was determined using ELISA. The data represents the mean±SD from triplicates. ^*P<0.05; significant difference between W/S and GK rats. ^**P<0.05; significant difference between non-exercise group and exercise group per rat type.

Figure 5

Effect of short-term swimming exercise on the serum C-peptide concentration. Serum was harvested from the blood samples collected from the abdominal veins of the W/S and GK rats. C-peptide level was determined using a C-peptide ELISA kit. The data represents the mean±SD from triplicates.

Figure 6

Effect of short-term swimming exercise on insulin-degrading enzyme (IDE) expression. IDE expression in the liver was detected with anti-IDE primary antibody and horseradish peroxidase-conjugated goat anti-rabbit IgG as described in Materials and Methods. The densitometric intensity of the IDE protein band was determined. The data represents the mean±SD from triplicates. ^*P<0.05; significant difference between W/S and GK rats.