Limits...
TRB3 gene silencing alleviates diabetic cardiomyopathy in a type 2 diabetic rat model.

Ti Y, Xie GL, Wang ZH, Bi XL, Ding WY, Wang J, Jiang GH, Bu PL, Zhang Y, Zhong M, Zhang W - Diabetes (2011)

Bottom Line: We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased.These anatomic findings were accompanied by significant improvements in cardiac function.Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Ji’nan, Shandong Province, China.

ABSTRACT

Objective: Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved.

Research design and methods: The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM.

Results: Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased.

Conclusions: TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM.

Show MeSH

Related in: MedlinePlus

Diabetic (DM) rats show metabolic disturbance. A: Total cholesterol (TC) levels. B: Triglyceride (TG) levels. C: FFAs. D: FBG. E: Fasting insulin (FINS). F: ISI. Data are mean ± SEM; n = 7–10 per group. *P < 0.05 vs. control; †P < 0.05 vs. HF; #P < 0.05 vs. chow + STZ. w, weeks.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3198078&req=5

Figure 1: Diabetic (DM) rats show metabolic disturbance. A: Total cholesterol (TC) levels. B: Triglyceride (TG) levels. C: FFAs. D: FBG. E: Fasting insulin (FINS). F: ISI. Data are mean ± SEM; n = 7–10 per group. *P < 0.05 vs. control; †P < 0.05 vs. HF; #P < 0.05 vs. chow + STZ. w, weeks.

Mentions: The biochemical values are given in Fig. 1. After 4 weeks of an HF diet, serum triglyceride and FFA levels were significantly higher in the HF and diabetic groups than in the control and chow + STZ groups (P < 0.05). The ISI was markedly decreased in the HF and diabetic groups (P < 0.05). Insulin resistance appeared at week 4 in rats fed an HF diet. One week after STZ injection, FBG was remarkably elevated in the diabetic group and remained elevated until the end of the experiment. ISI consistently decreased in the diabetic group after the onset of diabetes. Simultaneously, in the diabetic group, serum total cholesterol, total triglyceride, and FFA levels were maintained at higher levels than the control (P < 0.05) during diabetes. Thus, the diabetic model induced by an HF diet and low-dose STZ was characterized by insulin resistance, moderate hyperglycemia, and hyperlipidemia, resembling the state of chemical diabetes in humans.


TRB3 gene silencing alleviates diabetic cardiomyopathy in a type 2 diabetic rat model.

Ti Y, Xie GL, Wang ZH, Bi XL, Ding WY, Wang J, Jiang GH, Bu PL, Zhang Y, Zhong M, Zhang W - Diabetes (2011)

Diabetic (DM) rats show metabolic disturbance. A: Total cholesterol (TC) levels. B: Triglyceride (TG) levels. C: FFAs. D: FBG. E: Fasting insulin (FINS). F: ISI. Data are mean ± SEM; n = 7–10 per group. *P < 0.05 vs. control; †P < 0.05 vs. HF; #P < 0.05 vs. chow + STZ. w, weeks.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198078&req=5

Figure 1: Diabetic (DM) rats show metabolic disturbance. A: Total cholesterol (TC) levels. B: Triglyceride (TG) levels. C: FFAs. D: FBG. E: Fasting insulin (FINS). F: ISI. Data are mean ± SEM; n = 7–10 per group. *P < 0.05 vs. control; †P < 0.05 vs. HF; #P < 0.05 vs. chow + STZ. w, weeks.
Mentions: The biochemical values are given in Fig. 1. After 4 weeks of an HF diet, serum triglyceride and FFA levels were significantly higher in the HF and diabetic groups than in the control and chow + STZ groups (P < 0.05). The ISI was markedly decreased in the HF and diabetic groups (P < 0.05). Insulin resistance appeared at week 4 in rats fed an HF diet. One week after STZ injection, FBG was remarkably elevated in the diabetic group and remained elevated until the end of the experiment. ISI consistently decreased in the diabetic group after the onset of diabetes. Simultaneously, in the diabetic group, serum total cholesterol, total triglyceride, and FFA levels were maintained at higher levels than the control (P < 0.05) during diabetes. Thus, the diabetic model induced by an HF diet and low-dose STZ was characterized by insulin resistance, moderate hyperglycemia, and hyperlipidemia, resembling the state of chemical diabetes in humans.

Bottom Line: We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased.These anatomic findings were accompanied by significant improvements in cardiac function.Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Ji’nan, Shandong Province, China.

ABSTRACT

Objective: Tribbles 3 (TRB3) is associated with insulin resistance, an important trigger in the development of diabetic cardiomyopathy (DCM). We sought to determine whether TRB3 plays a major role in modulating DCM and the mechanisms involved.

Research design and methods: The type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of type 2 DCM by serial echocardiography and metabolite tests, Western blot analysis for TRB3 expression, and histopathologic analyses of cardiomyocyte density, lipids accumulation, cardiac inflammation, and fibrosis area. We then used gene silencing to investigate the role of TRB3 in the pathophysiologic features of DCM.

Results: Rats with DCM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, fibrosis, and TRB3 overexpression. We found that the silencing of TRB3 ameliorated metabolic disturbance and insulin resistance; myocardial hypertrophy, lipids accumulation, inflammation, fibrosis, and elevated collagen I-to-III content ratio in DCM rats were significantly decreased. These anatomic findings were accompanied by significant improvements in cardiac function. Furthermore, with TRB3 gene silencing, the inhibited phosphorylation of Akt was restored and the increased phosphorylation of extracellular signal-regulated kinase 1/2 and Jun NH(2)-terminal kinase in DCM was significantly decreased.

Conclusions: TRB3 gene silencing may exert a protective effect on DCM by improving selective insulin resistance, implicating its potential role for treatment of human DCM.

Show MeSH
Related in: MedlinePlus