Korean J Physiol Pharmacol.  2016 Nov;20(6):613-619. 10.4196/kjpp.2016.20.6.613.

Insulin-like growth factor-1 improves diabetic cardiomyopathy through antioxidative and anti-inflammatory processes along with modulation of Akt/GSK-3β signaling in rats

Affiliations
  • 1Center of Morphological Experiment, Medical College of Yanbian University, Yanji 133000, Jilin Province, China. dyxu@ybu.edu.cn

Abstract

Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-α and IL-1β), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-3β). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-3β. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-3β signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.

Keyword

Akt; Diabetic cardiomyopathy; GSK-3β; Insulin-like growth factor-1

MeSH Terms

Animals
Apoptosis
Blotting, Western
Body Weight
Diabetes Mellitus
Diabetic Cardiomyopathies*
Enzyme-Linked Immunosorbent Assay
Fibrosis
Glycogen Synthase Kinases
Humans
In Situ Nick-End Labeling
Inflammation
Insulin-Like Growth Factor I
Male
Oxidative Stress
Phosphorylation
Rats*
Rats, Wistar
Streptozocin
Glycogen Synthase Kinases
Insulin-Like Growth Factor I
Streptozocin

Figure

  • Fig. 1 IGF-1 attenuated pathological change in the heart of experimental diabetic rats.(A) Typical pictures of myocardial tissue sections of left ventricular specimens stained with hematoxylin and eosin (magnification=400×). n=8 per group. (B) Typical pictures of myocardial tissue sections stained with masson's trichrome (magnification=400×). Arrows in the figures indicate myocardial interstitial Fibrosis. n=8 per group. (C) Typical transmission electron micrographs (magnification=20000×). Arrows in the figures indicate mitochondrial damage, n=8 per group. (D) Ratio of fibrosis area to total area (%), n=8 per group; Data are mean±SEM. *p<0.05 vs. control group; #p<0.05 vs. DM group.

  • Fig. 2 IGF-1 relieves inflammatory markers in diabetic rats.(A) Levels of IL-1β. (B) Levels of TNF-α. Values are means±SEM; *p<0.05 vs. control group; #p<0.05 vs. DM group. Number of experiments, n=8 per group.

  • Fig. 3 IGF-1 elevates the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the heart of experimental diabetic rats.(A) Activity of SOD. (B) Content of MDA; Data are means±SEM; *p<0.05 vs. control group; #p<0.05 vs. MD group. Number of experiments, n=8 per group.

  • Fig. 4 IGF-1 attenuates apoptosis in the heart of experimental diabetic rats.(A) Typical pictures of myocardial tissue sections of left ventricular specimens stained with TUNEL (magnification=200×). Number of experiments, n=8 per group. I. Control group; II, DM group; III, DM+IGF-1 group. (B) The mean density of TUNEL stain. Number of experiment, n=8 per group. (C) The expression of Bcl-2 and Bax of experimental rats. Number of experiments, n=8 per group. Values are mean±SD. *p<0.05 vs. control group; #p<0.05 vs. DM group. Con, control group; DM, diabetic group; DM+IGF-1, DM+ IGF-1 group.

  • Fig. 5 IGF-1 activates Akt-GSK-3β signaling pathway in the heart of experimental diabetic rats.(A) p-Akt/Akt. (B) p-GSK-3β/GSK-3β; Values are means±SEM; *p<0.05 vs. control group; #p<0.05 vs. DM group. Number of experiments, n=8 per group.


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