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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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Related in: MedlinePlus

Comparison of plasma insulin (a) and C-peptide levels (b) among the experimental groups. 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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fig1: Comparison of plasma insulin (a) and C-peptide levels (b) among the experimental groups. 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 confirm the generation of a rat model of insulin-deficient diabetes, we determined plasma insulin and C-peptide levels at the end of the study. The mean plasma insulin levels of pancreatectomized rats were 7.6% (AL group) and 5.7% (R group) than that of the C group (Figure 1a; P<0.001 vs C group for both). The mean plasma C-peptide levels of pancreatectomized rats were 15.6% (AL group) and 8.6% (R group) than that of the C group (Figure 1b; P<0.001 vs C group for both). Insulin and C-peptide levels did not differ significantly between the AL and R groups.


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 plasma insulin (a) and C-peptide levels (b) among the experimental groups. 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

fig1: Comparison of plasma insulin (a) and C-peptide levels (b) among the experimental groups. 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 confirm the generation of a rat model of insulin-deficient diabetes, we determined plasma insulin and C-peptide levels at the end of the study. The mean plasma insulin levels of pancreatectomized rats were 7.6% (AL group) and 5.7% (R group) than that of the C group (Figure 1a; P<0.001 vs C group for both). The mean plasma C-peptide levels of pancreatectomized rats were 15.6% (AL group) and 8.6% (R group) than that of the C group (Figure 1b; P<0.001 vs C group for both). Insulin and C-peptide levels did not differ significantly between the AL and R groups.

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