Fig. 1Experimental design. Flow chart of the experimental design is shown. LETO, Long-Evans Tokushima Otsuka; OLETF, Otsuka Long Evans Tokushima Fatty.
Fig. 2Effects 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. 3Effects 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. 4Profiles 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. 5Glucose 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.
Table 1The characteristics of the experimental groups after 28 weeks of treatment (at 40 weeks of age) with rosiglitazone, exercise, and combined rosiglitazone and exercise
Characteristic |
LETO |
OC |
OR |
OEx |
OREx |
No. |
7 |
7 |
7 |
7 |
7 |
Glucose, mmol/L |
5.63 (5.49–5.85) |
7.27 (6.74–7.74)a
|
6.07 (5.99–6.38)b
|
6.24 (5.63–6.66)b
|
5.99 (5.67–6.14)b
|
Insulin, ng/mL |
3.24 (2.90–3.51) |
7.75 (7.38–8.40)a
|
2.65 (2.35–3.73)b
|
3.82 (3.07–4.78)b
|
2.43 (2.06–2.87)b
|
Adiponectin, µg/mL |
1.55 (1.27–1.63) |
1.50 (1.35–1.61)a
|
4.35 (3.67–4.63)b
|
1.72 (1.49–1.79)c
|
2.77 (2.57–3.73)b
|
Leptin, ng/mL |
2.91 (2.39–3.44) |
15.85 (15.31–16.55)a
|
17.15 (15.45–17.15)a
|
8.90 (5.60–9.35)b,c
|
10.66 (9.00–15.36)a
|
Total cholesterol, mmol/L |
2.59 (2.50–2.72) |
3.05 (2.97–3.13) |
2.52 (2.30–2.99)b
|
2.62 (2.32–2.97) |
2.40 (2.35–2.45)b
|
HDL-C, mmol/L |
0.76 (0.74–0.78) |
0.91 (0.82–0.95) |
0.82 (0.76–0.86) |
0.82 (0.76–0.93) |
0.81 (0.78–0.85) |
Triglycerides, mmol/L |
0.35 (0.31–0.61) |
1.63 (1.43–1.72)a
|
0.42 (0.34–0.76)b
|
0.74 (0.51–0.81) |
0.51 (0.48–0.58)b
|
Free fatty acid, g/L |
0.26 (0.25–0.28) |
0.33 (0.32–0.34) |
0.28 (0.26–0.31) |
0.31 (0.30–0.33) |
0.31 (0.27–0.34) |
HOMA-IR |
21.23 (17.80–23.94) |
59.07 (54.38–69.16)a
|
17.70 (17.19–22.11)b
|
29.29 (21.43–31.64)b
|
16.08 (13.79–20.78)b
|
Table 2Effects of rosiglitazone and exercise on body composition at 30 weeks of age
Variable |
LETO |
OC |
OR |
OEx |
OREx |
No. |
7 |
7 |
7 |
7 |
7 |
Total mass, g |
499.6 (466.4–532.5) |
644.4 (601.4–682.0)a
|
678.7 (639.0–736.1)a
|
619.6 (583.8–639.9)a,b
|
624.7 (576.6–647.9)a,b
|
Lean body mass, g |
427.2 (406.9–440.4) |
438.9 (433.9–456.8) |
419.5 (399.6–433.4)c
|
463.3 (456.9–467.8)a,b
|
450.5 (447.0–457.4)a,b
|
Fat mass, g |
74.0 (42.7–79.2) |
195.7 (143.5–216.2)a
|
226.7 (214.9–295.1)a,c
|
146.3 (109.5–161.0)a,b
|
163.1 (109.0–175.6)a,b
|