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Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats.

Lee JH, Lee JH, Jin M, Han SD, Chon GR, Kim IH, Kim S, Kim SY, Choi SB, Noh YH - Exp. Mol. Med. (2014)

Bottom Line: To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12).R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively).In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Konkuk University School of Medicine, Seoul, Republic of Korea.

ABSTRACT
Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

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Comparison of weights of organs and tissues among the experimental groups. Heart (a), liver (b), both kidneys (c), both soleus muscle tissues (d) and both epididymal fat tissues (e). Data are presented as means±s.d. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. White bars: C, control (sham operation) rats; black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period.
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fig3: Comparison of weights of organs and tissues among the experimental groups. Heart (a), liver (b), both kidneys (c), both soleus muscle tissues (d) and both epididymal fat tissues (e). Data are presented as means±s.d. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. White bars: C, control (sham operation) rats; black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period.

Mentions: To determine whether reduced body weight due to insulin deficiency and/or diet control was accompanied by decreased weight of organs and tissues, we weighed the heart, liver, both epididymal fat pads, both kidneys and both soleus muscle tissues of all rats at the end of the study. Figure 3a shows that the mean heart weights of the AL group (1.33±0.20 g) and R group (1.02±0.20 g) were 80 and 61%, respectively, that of the C group (1.66±0.15 g; P<0.001 for both). It is noteworthy that the mean heart weight of the R group was only 77% that of the AL group (P<0.001). Figure 3b shows that the mean liver weight of the R group (8.3±2.2 g) was 50% that of the C group (16.7±3.8 g) and 54% that of the AL group (15.4±1.9 g; P<0.001 for both); the C and AL groups did not differ significantly. Figure 3c shows that the mean weight of both kidneys of the AL group (5.43±0.61 g) was 163% that of the C group (3.33±0.30 g) and 189% that of the R group (2.86±0.38 g; P<0.001 for both); the C and R groups did not differ significantly. Figure 3d shows that the mean weights of both soleus muscle tissues of the AL group (0.364±0.049 g) and R group (0.318±0.063 g) were 77 and 67%, respectively, that of C group (0.471±0.047 g; P<0.001 for both); the AL and R groups did not differ significantly. Figure 3e shows that the mean weights of both epididymal fat pads of the AL group (3.4±1.5 g) and R group (1.4±1.1 g) were 20 and 8%, respectively, that of C group (16.9±4.3 g; P<0.001 for both); the AL and R groups did not differ significantly. In pancreatectomized rats, the weights of all organs and tissues examined were significantly correlated with body weights and plasma insulin levels (Table 2).


Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats.

Lee JH, Lee JH, Jin M, Han SD, Chon GR, Kim IH, Kim S, Kim SY, Choi SB, Noh YH - Exp. Mol. Med. (2014)

Comparison of weights of organs and tissues among the experimental groups. Heart (a), liver (b), both kidneys (c), both soleus muscle tissues (d) and both epididymal fat tissues (e). Data are presented as means±s.d. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. White bars: C, control (sham operation) rats; black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150935&req=5

fig3: Comparison of weights of organs and tissues among the experimental groups. Heart (a), liver (b), both kidneys (c), both soleus muscle tissues (d) and both epididymal fat tissues (e). Data are presented as means±s.d. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. White bars: C, control (sham operation) rats; black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period.
Mentions: To determine whether reduced body weight due to insulin deficiency and/or diet control was accompanied by decreased weight of organs and tissues, we weighed the heart, liver, both epididymal fat pads, both kidneys and both soleus muscle tissues of all rats at the end of the study. Figure 3a shows that the mean heart weights of the AL group (1.33±0.20 g) and R group (1.02±0.20 g) were 80 and 61%, respectively, that of the C group (1.66±0.15 g; P<0.001 for both). It is noteworthy that the mean heart weight of the R group was only 77% that of the AL group (P<0.001). Figure 3b shows that the mean liver weight of the R group (8.3±2.2 g) was 50% that of the C group (16.7±3.8 g) and 54% that of the AL group (15.4±1.9 g; P<0.001 for both); the C and AL groups did not differ significantly. Figure 3c shows that the mean weight of both kidneys of the AL group (5.43±0.61 g) was 163% that of the C group (3.33±0.30 g) and 189% that of the R group (2.86±0.38 g; P<0.001 for both); the C and R groups did not differ significantly. Figure 3d shows that the mean weights of both soleus muscle tissues of the AL group (0.364±0.049 g) and R group (0.318±0.063 g) were 77 and 67%, respectively, that of C group (0.471±0.047 g; P<0.001 for both); the AL and R groups did not differ significantly. Figure 3e shows that the mean weights of both epididymal fat pads of the AL group (3.4±1.5 g) and R group (1.4±1.1 g) were 20 and 8%, respectively, that of C group (16.9±4.3 g; P<0.001 for both); the AL and R groups did not differ significantly. In pancreatectomized rats, the weights of all organs and tissues examined were significantly correlated with body weights and plasma insulin levels (Table 2).

Bottom Line: To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12).R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively).In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Konkuk University School of Medicine, Seoul, Republic of Korea.

ABSTRACT
Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

Show MeSH
Related in: MedlinePlus