Limits...
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.

Show MeSH

Related in: MedlinePlus

Comparison of the sequential changes in the rate of daily food intake (g per kg body weight per day) throughout the experiment (a), comparison of the rate of daily food intake during the induction period of diabetes after surgery (b) and during the diet control period (c). Comparison of the sequential changes in fasting blood glucose (FBG) levels throughout the experiment (d), comparison of FBG levels during the induction period of diabetes after surgery (e) and at the last week of the diet control period (f). Comparison of the sequential changes in body weights throughout the experiment (g), comparison of body weights during the induction period of diabetes after surgery (h) and during the diet control period (i). Data are presented as means±s.d.. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. Open circles and white bars: C, control (sham operation) rats; filled squares and black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed triangles and dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period. *P<0.05, **P<0.001 vs C; †P<0.001, ††P<0.05 vs AL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150935&req=5

fig2: Comparison of the sequential changes in the rate of daily food intake (g per kg body weight per day) throughout the experiment (a), comparison of the rate of daily food intake during the induction period of diabetes after surgery (b) and during the diet control period (c). Comparison of the sequential changes in fasting blood glucose (FBG) levels throughout the experiment (d), comparison of FBG levels during the induction period of diabetes after surgery (e) and at the last week of the diet control period (f). Comparison of the sequential changes in body weights throughout the experiment (g), comparison of body weights during the induction period of diabetes after surgery (h) and during the diet control period (i). Data are presented as means±s.d.. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. Open circles and white bars: C, control (sham operation) rats; filled squares and black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed triangles and dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period. *P<0.05, **P<0.001 vs C; †P<0.001, ††P<0.05 vs AL.

Mentions: As shown in Figure 2a, the rate of daily food intake did not differ significantly among the groups during the 2-week acclimation period (C group 78.2±16.4, AL group 80.0±17.2, R group 76.9±15.5 g per kg body weight per day; P=0.893). However, the rate of daily food intake in the C group decreased over time (58.9±13.5 g per kg body weight per day during the 5-week diabetes induction period), whereas that of the pancreatectomized rats fed ad libitum for 5 weeks after surgery increased significantly (AL group 95.1±43.0, R group 93.9±39.3 g per kg body weight per day; P<0.001 vs C group for both; Figure 2b). Rats in the AL group ate about three times more than rats in the C and R groups during the diet control period (P<0.001; Figure 2c).


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 the sequential changes in the rate of daily food intake (g per kg body weight per day) throughout the experiment (a), comparison of the rate of daily food intake during the induction period of diabetes after surgery (b) and during the diet control period (c). Comparison of the sequential changes in fasting blood glucose (FBG) levels throughout the experiment (d), comparison of FBG levels during the induction period of diabetes after surgery (e) and at the last week of the diet control period (f). Comparison of the sequential changes in body weights throughout the experiment (g), comparison of body weights during the induction period of diabetes after surgery (h) and during the diet control period (i). Data are presented as means±s.d.. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. Open circles and white bars: C, control (sham operation) rats; filled squares and black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed triangles and dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period. *P<0.05, **P<0.001 vs C; †P<0.001, ††P<0.05 vs AL.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Comparison of the sequential changes in the rate of daily food intake (g per kg body weight per day) throughout the experiment (a), comparison of the rate of daily food intake during the induction period of diabetes after surgery (b) and during the diet control period (c). Comparison of the sequential changes in fasting blood glucose (FBG) levels throughout the experiment (d), comparison of FBG levels during the induction period of diabetes after surgery (e) and at the last week of the diet control period (f). Comparison of the sequential changes in body weights throughout the experiment (g), comparison of body weights during the induction period of diabetes after surgery (h) and during the diet control period (i). Data are presented as means±s.d.. The data were analyzed using one-way analysis of variance with Tukey's post hoc test. Open circles and white bars: C, control (sham operation) rats; filled squares and black bars: AL, pancreatectomized diabetic rats fed ad libitum; dashed triangles and dashed bars: R, pancreatectomized diabetic rats fed a calorie-controlled diet during the diet control period. *P<0.05, **P<0.001 vs C; †P<0.001, ††P<0.05 vs AL.
Mentions: As shown in Figure 2a, the rate of daily food intake did not differ significantly among the groups during the 2-week acclimation period (C group 78.2±16.4, AL group 80.0±17.2, R group 76.9±15.5 g per kg body weight per day; P=0.893). However, the rate of daily food intake in the C group decreased over time (58.9±13.5 g per kg body weight per day during the 5-week diabetes induction period), whereas that of the pancreatectomized rats fed ad libitum for 5 weeks after surgery increased significantly (AL group 95.1±43.0, R group 93.9±39.3 g per kg body weight per day; P<0.001 vs C group for both; Figure 2b). Rats in the AL group ate about three times more than rats in the C and R groups during the diet control period (P<0.001; Figure 2c).

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