ABSTRACT
Metabolic syndrome, characterized by centralobesity, hypertension, bycentralobesity, hypertension, and hyperlipidemia, increases the incidence and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that the accumulation of hepatic fatty acid can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria are the major sites of fatty acid β-oxidation, which is the major degradation mechanism of fatty acids. Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid-induced hepatic insulin resistance. Mitochondrial autophagy (mitophagy), a catabolic process, selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function. Therefore, mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance. Here, we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance. Additionally, we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome.
ABSTRACT
AIM: To study the protective effect and mechanism of swimming on kidney of diabetic mice. METHODS: The mice were randomly divided into normal control group, normal swimming group, type 2 diabetes mellitus (T2DM) mice model group, diabetic swimming group and metformin group. T2DM model was established by streptozotocin (STZ) method. The mice in normal swimming group and diabetic swimming group were given swimming exercise (1 h a day), and the metformin group were given metformin (200 mg/kg) by gavage once a day for 7 weeks. Fasting blood glucose and serum insulin were measured and insulin resistance index was calculated. The contents of uric acid, urea and creatinine in serum were determined. The ratio of renal mass to body mass was calculated, and the pathological changes of renal tissues were observed. The relative expressions of autophagy related proteins LC3 and P62 in renal tissues were detected by Western blot. RESULTS: Compared with normal control group, insulin resistance index and renal mass/body mass ratio in model group were significantly increased. Serum uric acid, urea and creatinine levels increased, and glomerular pathological changes were obvious. LC3II/LC3I ratio decreased significantly. The expression of P62 was significantly increased. Compared with model group, insulin resistance index and renal mass/body mass ratio in diabetic swimming group were significantly decreased. The contents of serum uric acid, urea and creatinine decreased, and the pathological changes of glomerular were alleviated. LC3II/LC3I ratio increased significantly. The expression of P62 decreased significantly (P even <0.05). CONCLUSION: Swimming protects the kidney injury of T2DM mice, and its mechanism may be related to promoting the autophagy process of renal tissue.
ABSTRACT
Aim To study the effects of eugenol on hypoglycemic effect and hepatic glucose and lipid metabolism in type 2 diabetic mice, and to explore the possible mechanism. Methods The model of type 2 diabetes induced by long term high-fat diet was divided into four groups. The blood glucose and body weight of each group were measured once a week. After six weeks, the liver tissues of mice in each group were dissected and the liver mass and body mass of mice were weighed. Liver index, lipid metabolism and liver function were measured. Oral glucose tolerance test was performed. The levels of blood glucose, insulin, triglyceride, cholesterol, resistin, leptin, auxin, glucagon and plasminogen activator inhibitor-1 in serum were measured. He staining was used to observe the pathological changes of liver tissues. The expressions of SHP, pfoxo1, pCREB, PEPCK and G6Pase proteins in liver were detected by Western blot. Results Compared with HFD group, E40 group had lower body weight, smaller liver volume and healthy dark red. Compared with HFD group, E40 group decreased liver index, lipid metabolism and liver function. OGTT test showed that glucose tolerance was enhanced and the area under the curve was decreased in E40 group compared with HFD group. The levels of blood glucose, insulin, triglyceride, resistin, leptin, glucagon and plasminogen activator inhibitor-1 in E40 group were lower than those in HFD group. He staining showed that hepatocytes in HFD group were larger and accompanied with bullous steatosis than those in RD group. Hepatocyte steatosis and liver pathological state were significantly improved in E40 group. The results of Western blot showed that compared with HFD group, the expression of SHP, pfoxo1 and pCREB protein in E40 group was up-regulated, and the expression of PEPCK and G6Pase protein was down-regulated. Conclusions Eugenol can regulate the SHP/pFOXO1/PCREB/PEPCK/G6Pase signaling pathway, regulate glucose and lipid metabolism, inhibit insulin resistance, improve blood glucose level and glucose and lipid metabolism disorders in type 2 diabetes mellitus.