Diabetes Metab J.  2017 Dec;41(6):474-485. 10.4093/dmj.2017.41.6.474.

Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats

Affiliations
  • 1Department of Internal Medicine, Inha University School of Medicine, Incheon, Korea. namms@inha.ac.kr
  • 2Qingdao Endocrine and Diabetes Hospital, Qingdao, China.
  • 3Department of Biomedical Sciences, Inha University School of Medicine, Incheon, Korea.
  • 4Department of Anatomy, Inha University School of Medicine, Incheon, Korea. sunpark@inha.ac.kr

Abstract

BACKGROUND
Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals.
METHODS
We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment.
RESULTS
Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group.
CONCLUSION
Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.

Keyword

Beta-cell; Body composition; Diabetes; Exercise; Rats, inbred OLETF; Rosiglitazone

MeSH Terms

Animals
Body Composition
Diabetes Mellitus, Type 2
Exercise*
Fasting
Glucose*
Metabolism*
Rats, Inbred OLETF*
Thiazolidinediones
Weight Gain
Glucose
Thiazolidinediones

Figure

  • Fig. 1 Experimental design. Flow chart of the experimental design is shown. LETO, Long-Evans Tokushima Otsuka; OLETF, Otsuka Long Evans Tokushima Fatty.

  • Fig. 2 Effects of rosiglitazone and exercise treatments on glucose tolerance. Time course of blood glucose during the intraperitoneal glucose tolerance test is reported at (A) 12 weeks, (B) 24 weeks, and (C) 40 weeks of age. (D) The area under the curve (AUC) for glucose at 40 weeks were calculated. Values are presented as mean±standard error (n=7). LETO, Long-Evans Tokushima Otsuka; OC, Otsuka Long Evans Tokushima Fatty (OLETF) rats with no treatment; OR, OLETF rats with rosiglitazone treatment only; OEx, OLETF rats with exercise only; OREx, OLETF rats with combined treatment of rosiglitazone and exercise. aP<0.05 vs. OC, bP<0.01 vs. OC, cP<0.05, dP<0.01 vs. LETO.

  • Fig. 3 Effects of rosiglitazone and exercise on body weight and epididymal fat weight. (A) Body weight and (C) epididymal fat weight at 12 and 40 weeks are shown. Values are presented as mean±standard error (n=7). The change ratio of (B) body weight and (D) epididymal fat weight from 12 to 40 weeks were calculated. Each box (n=7) are presented as median (interquartile range). LETO, Long-Evans Tokushima Otsuka; OC, Otsuka Long Evans Tokushima Fatty (OLETF) rats with no treatment; OR, OLETF rats with rosiglitazone treatment only; OEx, OLETF rats with exercise only; OREx, OLETF rats with combined treatment of rosiglitazone and exercise. aP<0.05 vs. LETO, bP<0.01 vs. LETO, cP<0.01 vs. OC, dP<0.01, eP<0.001.

  • Fig. 4 Profiles of the pancreatic islets in rosiglitazone, exercise, and combined treatment. (A) Chronological changes of pancreatic islets in LETO rats and OLETF rats with and without anti-diabetic treatment are presented with insulin immunostaining at 12, 24, and 40 weeks. (B) Changes in islet alterations by percentage at 40 weeks. The number of the altered islets was counted in the pancreatic tissues and the ratio was calculated. Each box (n=7×2 sections) are presented as median (interquartile range). (C) β-Cell number of the total area of the pancreas was calculated at 40 weeks. The pancreatic islet area was measured using Quantity One (Bio-Rad). (D) In situ hybridization: insulin mRNA in LETO, OC, OR, OEx, and OREx groups at 40 weeks. LETO, Long-Evans Tokushima Otsuka; OC, Otsuka Long Evans Tokushima Fatty (OLETF) rats with no treatment; OR, OLETF rats with rosiglitazone treatment only; OEx, OLETF rats with exercise only; OREx, OLETF rats with combined treatment of rosiglitazone and exercise. aP<0.001 vs. LETO, bP<0.01 vs. OC, cP<0.001 vs. OC, dP<0.01.

  • Fig. 5 Glucose transporter 2 (GLUT-2) expression in pancreatic islets with rosiglitazone, exercise, and combined treatment at 40 weeks. The pancreatic tissues were immunolabeled for insulin (green fluorescence in upper panel) and GLUT-2 (red fluorescence in middle panel). The immunofluorescent signals were merged and are shown in the lower panel. LETO, Long-Evans Tokushima Otsuka; OC, Otsuka Long Evans Tokushima Fatty (OLETF) rats with no treatment; OR, OLETF rats with rosiglitazone treatment only; OEx, OLETF rats with exercise only; OREx, OLETF rats with combined treatment of rosiglitazone and exercise.


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