Effects of adipokine chemerin on the improvement of islet function in diabetic mice by aerobic exercise and its mechanisms

Abstract

Objective: To investigate the effects of adipokines chemerin on the improvement of islet function caused by exercise in mice with diabetes, and the possible mechanism of glucagon-like peptide 1 (GLP-1). Methods: Male ICR mice were randomly divided into a control group fed with normal diet (Con, n=6) and a diabetic modeling group fed with 60% kcal high-fat diet (n=44). After 6 weeks, the diabetic modeling group was once given a fasting intraperitoneal injection of streptozotocin (100 mg/kg). The successfully modeled mice were divided into diabetes group (DM), diabetes plus exercise group (EDM), and diabetes plus exercise and exogenous chemerin group (EDMC), 6 in each group. Mice in exercise groups participated in a six-week modest intensity treadmill running exercise with a gradually increased load. Mice in the EDMC group were intraperitoneally injected with exogenous chemerin (8 μg/kg) from the 4th week of the exercise period, six days per week, and one time per day. And the other groups were untreated. Adipose chemerin knockout mice were constructed. Then they and the control mice were divided into 6 groups (n=4): Normal diet control group (Con-ND), Normal diet chemerin knockout heterozygote mice group (Chemerin(+/-)-ND), Normal diet chemerin knockout homozygotes mice group(Chemerin(-/-)-ND), High-fat diet control group (Con-HFD), High-fat diet chemerin knockout heterozygote mice group (Chemerin(+/-)-HFD), High-fat diet chemerin knockout homozygotes mice group (Chemerin(-/-)-HFD). They were fed with normal or high-fat diet for 11 weeks and oral glucose tolerance test (OGTT) was conducted. After the mice of each group were executed under anesthesia, the samples such as pancreas and colon were collected. Fasting blood glucose (FBG) and fasting insulin (FINS) levels in mice were measured, and the insulin resistance index (HOMA-IR) was calculated. HE staining was used to observe the structure of islets. ELISA was used to detect the GLP-1 level in serum. The mRNA levels of proglucagon (GCG) and chemerin in the colon were measured by real-time PCR. And the protein levels of GCG and chemerin in the colon were detected by Western blot. Results: Compared with the DM group, the vacuolar degeneration and shrinkage of islet cells in the EDM group were reduced, the islet structure was improved, while the levels of FINS, HOMA-IR and FBG were decreased significantly (P＜0.05 or P＜0.01). The colon and serum chemerin levels were decreased significantly(P＜0.05), while the colonic GCG mRNA and protein levels were increased significantly (P＜0.05 or P＜0.01). Compared with the EDM group, the islet cells in the EDMC group were shrunken, with unclear borders. The structure of the islets was damaged, and the levels of FINS, HOMA-IR and FBG were increased significantly (P＜0.01), while the mRNA and protein levels of GCG were decreased significantly (P＜0.05 or P＜0.01). Compared with the Con-HFD group, the blood glucose at 30, 90 and 120 min after oral glucose in the chemerin (-/-)-HFD group was significantly lower (P＜0.01), and the area under the blood glucose time curve was significantly lower (P＜0.01). The islets had clear structure, regular shape and well-defined boundaries, while the serum GLP-1 and colonic GCG protein levels were increased significantly(P＜0.05). Conclusion: Aerobic exercise improves the structure and function of pancreatic islets by reducing the level of chemerin in diabetes mice, which is related to the negative regulation of chemerin on GLP-1 level.