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Objective@#To investigate the effects of metformin treatment on fatty acid metabolism and expression and activity of AMP-activated protein kinase (AMPK)α in skeletal muscle in type 2 diabetes.@*Methods@#A total of 30 cases with or without type 2 diabetes mellitus (T2DM) who received selective surgery were enrolled from department of orthopaedics. These patients were divided into three groups: DM group, DM+ MET group and NC group. Blood samples were drawn from an antecubial vein for measurement of plasma glucose, insulin, lipid and free fatty acid (FFA). Insulin sensitivity index (ISI) was calculated. Skeletal muscle was freezed in liquid nitrogen during orthopaedics surgery and was kept at -70 ℃ until assay. Skeletal muscle tissue was analysed en bloc for triglyceride, long chain fatty acyl-CoA (LCACoAs), AMPKα1 and AMPKα2 mRNA expression [quantitative real-time polymerase chain reaction (qRT-PCR)], as well as protein expression of AMPKα1, AMPKα2 and phosphorylated AMPKα (p-AMPKα) (Western blot).@*Results@#⑴ Compared with NC group, HbA1c, fasting blood glucose (FBG), fasting insulin (FINS), FFA and triglyceride(TG) were increased in DM group, while metformin treatment decreased FFA and TG; ISI was reduced in DM group than that in NC group, but ISI was higher in DM+ MET group compared with DM group (P<0.05 or P<0.01). ⑵ The contents of triglyceride and LCACoAs in skeletal muscle in DM group were higher than those in NC group, while those in DM + MET group were lower than those in DM group (P<0.05 ). ⑶ No alternations of mRNA levels and protein levels of AMPKα1 were detected among three groups (P>0.05). Compared with NC group, AMPKα2 mRNA expression and protein levels of AMPKα2 and p-AMPKα in skeletal muscle were decreased in DM group, while metformin treatment increased protein level of p-AMPKα (P<0.05).@*Conclusions@#Compared with NC group, muscle lipid accumulation and insulin resistance always exist in T2DM patients. Metformin treatment may increase activity of AMPKα, resulting in a decrease in lipid accumulation in skeletal muscle and increase insulin sensitivity in T2DM patients.
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Objective To investigate the effects of metformin treatment on fatty acid metabolism and expression and activity of AMP-activated protein kinase (AMPK)α in skeletal muscle in type 2 diabetes.Methods A total of 30 cases with or without type 2 diabetes mellitus (T2DM) who received selective surgery were enrolled from department of orthopaedics.These patients were divided into three groups:DM group,DM + MET group and NC group.Blood samples were drawn from an antecubial vein for measurement of plasma glucose,insulin,lipid and free fatty acid (FFA).Insulin sensitivity index (ISI) was calculated.Skeletal muscle was freezed in liquid nitrogen during orthopaedics surgery and was kept at-70 ℃ until assay.Skeletal muscle tissue was analysed en bloc for triglyceride,long chain fatty acyl-CoA (LCACoAs),AMPKα1 and AMPKα2 mRNA expression [quantitative real-time polymerase chain reaction (qRT-PCR)],as well as protein expression of AMPKα1,AMPKα2 and phosphorylated AMPKα (p-AMPKα) (Western blot).Results (1) Compared with NC group,HbA1c,fasting blood glucose (FBG),fasting insulin (FINS),FFA and triglyceride(TG) were increased in DM group,while metformin treatment decreased FFA and TG;ISI was reduced in DM group than that in NC group,but ISI was higher in DM + MET group compared with DM group (P ＜0.05 or P ＜0.01).(2) The contents of triglyceride and LCACoAs in skeletal muscle in DM group were higher than those in NC group,while those in DM + MET group were lower than those in DM group (P ＜0.05).(3) No alternations of mRNA levels and protein levels of AMPKα1 were detected among three groups (P ＞ 0.05).Compared with NC group,AMPKα2 mRNA expression and protein levels of AMPKα2 and p-AMPKα in skeletal muscle were decreased in DM group,while metformin treatment increased protein level of p-AMPKα (P ＜ 0.05).Conclusions Compared with NC group,muscle lipid accumulation and insulin resistance always exist in T2DM patients.Metformin treatment may increase activity of AMPKα,resulting in a decrease in lipid accumulation in skeletal muscle and increase insulin sensitivity in T2DM patients.
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Objective To investigate the effects of high-fat diet on fatty acid metabolism, expression and activity of acetyl coenzyme A carboxylase (ACC) in skeletal muscle in rats. Methods Male Wistar rats aged 22-24 months were randomly divided into old control (OC) group and high-fat diet (HF) group. Male Wistar rats aged 4-5 months were selected as young control (YC) group. The rats in OC and YC groups were fed with basic diet, and the rats in HF group received high-fat diet. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. Skeletal muscle triglyceride was extracted and measured by an automated biochemistry analyzer. Long-chain acetyl coenzyme A (LCACoAs) were extracted from muscle and measured by a fluorospectrophotometer. Protein expressions of ACC and P-ACC were measured using SDS-PAGE and Western blot techniques. Results (1)Fasting blood glucose (FBG), fasting insulin (FINS) and free fatty acid were higher in OC group than in YC group and they increased significantly in HF group. Triglyceride (TG) and total cholesterol (TO levels were also elevated after high-fat feeding. (2)Glucose infusion rates (GIR) were reduced in OC group than in YC group, and decreased significantly after high-fat feeding. GIR was lower at the end of the 8th week than at the end of the 4th week in HF group. (3) Compared with YC group, skeletal muscle triglyceride and LCACoAs increased in OC group and increased significantly in HF group. (4)No alterations of protein levels of ACC in skeletal muscle were detected among three groups (P>0.05). The protein levels of P-ACC in skeletal muscle were lower in OC group, and much lower in HF group than in YC group (P<0.05 or P<0.01). Conclusions Compared with young rats, abnormal fatty acid metabolism and insulin resistance always exist in aged rats. High-fat feeding results in a significant increase in lipid content in skeletal muscle. Alterations of ACC activity may contribute to fat accumulation in skeletal muscle and insulin resistance.
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Objective To investigate the effects of high-fat diet on fatty acid metabolism in liver and insulin sensitivity in aged rats and to explore the mechanisms of insulin resistance associated with aging. Methods Male Wistar rats aged 22-24 months were randomly divided into old control (OC) group and high-fat diet (HF) group. Male Wistar rats aged 4-5 months were selected as young control (YC) group. The rats in OC and YC were fed with basic diet, and the rats in HF group received high fat diet. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. Extracted liver triglyceride was measured by an automated biochemistry analyzer. Results (1) Compared with YC group, fasting blood glucose(FBG), fasting insulin(FINS) and free fatty acid were increased in OC group and were increased significantly in HF group. Triglyceride(TG) and total cholesterol(TC) levels were also elevated in HF group. (2) Compared with YC group, glucose infusion rate (GIR) was reduced in OC group and was decreased significantly in HF group. GIR was lower at the end of the 8th week than that at the end of the 4th week in HF group. (3) Compared with YC group, liver triglyceride was increased in OC group and was increased significantly in HF group. Liver triglyceride was negatively correlated with GIR, and positively correlated with FBG. Conclusions Compared with young rats, abnormal fatty acid metabolism and insulin resistance always exist in aged rats. High-fat feeding results in a significant increase in lipid content in liver and more serious insulin resistance in aged rats. Lipid accumulation in liver may contribute to insulin resistance associated with aging and high-fat diet.
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Objective To investigate the relationship between l evels of FⅦc and features of IR as well as macrovascular complications in type 2 diabetes.Methods The 2001-10~2002-08 FⅦc levels were measured by a one -stage biological assay in patients with type 2 diabetes and controls.Results (1)Type 2 diabetic patients had significantly higher FⅦc than control subjects.(2)FⅦc levels were higher in the type 2 diabetes w ith macrovascular complications than in those without macrovascular complication s.(3)FⅦc levels correlated positively with most features of IR.Conclusion FⅦc levels are increased in type 2 diabetic pat ients.Elevated FⅦc may be an important sign of IR and may contribute to type 2 diabetes and its macrovascular diseases.
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0.05). But the determined values in the above two dose groups of Astragalus Injection were obviously lower than that in cisplatin group. There were remarkable differences.( P