AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with N...AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.展开更多
AIM:To evaluate the effects of soy supplementation on insulin resistance,fatty liver and alanine aminotransferase(ALT) levels in non-diabetic patients with chronic hepatitis C(CHC).METHODS:In a prospective,randomized ...AIM:To evaluate the effects of soy supplementation on insulin resistance,fatty liver and alanine aminotransferase(ALT) levels in non-diabetic patients with chronic hepatitis C(CHC).METHODS:In a prospective,randomized and singleblinded clinical trial,we compared patients with CHC who had casein as a supplement(n = 80)(control group),with patients who consumed a soy supplement diet(n = 80) [intervention group(IG)].Both groups received 32 g/d of protein for 12 wk.RESULTS:Patients' baseline features showed that 48.1% were overweight,43.7% had abdominal fat accumulation,34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance(HOMA-IR) ≥ 3.0.Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups;however,significant reductions in ALT levels occurred in the soy group.Multiple regression modeling indicated that in the presence of severe fibrosis(F3/F4),g glutamyl transferase elevation and high density lipoprotein(HDL) reduction,the intervention group had 75% less chance of developing hepatic steatosis(OR= 0.25;95% CI:0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal(ULN)(OR = 0.45,95% CI:0.22-0.89).Soy treatment did not have any effect on insulin resistance(OR = 1.92;95% CI:0.80-4.83),which might be attributed to the fact that the HOMAIR values at baseline in most of our patients were in the normal range.Advanced hepatic fibrosis,an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3.The IG group had a reduced risk of an ALT level > 1.5 × ULN.An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT.CONCLUSION:Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus(HCV) patients;it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance.It should be considered in the nutritional care of HCV patients.展开更多
Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed a...Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice,and exploring the potential molecular mechanisms.Insulin resistance in mice was induced with a high fat diet for 16 weeks.Animals were then treated with three different doses of baicalin(100,200,and 400 mg·kg^(-1)·d^(-1)for 14 weeks.Fasting blood glucose,fasting serum insulin,glucose tolerance test(GTT),insulin tolerance test(ITT),and skeletal muscle lipid deposition were measured.Additionally,the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated.Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance.Moreover,insulin resistance was significantly reversed.Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle.The properties of baicalin were mediated,at least in part,by inhibition of the AMPK/ACC pathway,a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway,a key regulator of Glycogen synthesis.These data suggest that baicalin,at dose up to 400 mg·kg^(-1)·d^(-1),is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage,through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.展开更多
Objective： To observe the effect of acupuncture on Akt2 mRNA expression in skeletal muscle of insulin resistant rat models. Methods： Twenty-four SD rats were randomly divided into a control group, a model group and ...Objective： To observe the effect of acupuncture on Akt2 mRNA expression in skeletal muscle of insulin resistant rat models. Methods： Twenty-four SD rats were randomly divided into a control group, a model group and an acupuncture group. Fasting plasma glucose （FPG）, fasting insulin （FINS）, insulin sensitivity index （ISI）, C peptide （C-P）, as well as Akt2 mRNA expression in skeletal muscle of rats were detected by glucose oxidase method, ELISA and real-time PCR. Results： Compared with the control group, the level of FP~ FINS and C-P increased significantly （P〈0.01） while ISI and Akt2 mRNA expression decreased markedly in the model group （P〈0.01, P〈0.05）. In the acupuncture group, the levels of FPC FINS and C-P were much lower than in the model group （P〈0.01, P〈0.01, P〈0.05） and ISI and Akt2 mRNA expression increased markedly （P〈0.01）. Conclusion： The mechanism of acupuncture in treating insulin resistance may relate to the up-regulated of the Akt2 mRNA expression and to the improvement of the signal transduction of PI3K pathway.展开更多
Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter p...Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.展开更多
文摘AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated.RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18expression and HOMA-R were signifi cantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH.
基金Supported by Gold Nutrition Indústria e Comercio and Centro colaborador Nordeste II/Ministério da Saúde,Brazil
文摘AIM:To evaluate the effects of soy supplementation on insulin resistance,fatty liver and alanine aminotransferase(ALT) levels in non-diabetic patients with chronic hepatitis C(CHC).METHODS:In a prospective,randomized and singleblinded clinical trial,we compared patients with CHC who had casein as a supplement(n = 80)(control group),with patients who consumed a soy supplement diet(n = 80) [intervention group(IG)].Both groups received 32 g/d of protein for 12 wk.RESULTS:Patients' baseline features showed that 48.1% were overweight,43.7% had abdominal fat accumulation,34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance(HOMA-IR) ≥ 3.0.Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups;however,significant reductions in ALT levels occurred in the soy group.Multiple regression modeling indicated that in the presence of severe fibrosis(F3/F4),g glutamyl transferase elevation and high density lipoprotein(HDL) reduction,the intervention group had 75% less chance of developing hepatic steatosis(OR= 0.25;95% CI:0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal(ULN)(OR = 0.45,95% CI:0.22-0.89).Soy treatment did not have any effect on insulin resistance(OR = 1.92;95% CI:0.80-4.83),which might be attributed to the fact that the HOMAIR values at baseline in most of our patients were in the normal range.Advanced hepatic fibrosis,an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3.The IG group had a reduced risk of an ALT level > 1.5 × ULN.An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT.CONCLUSION:Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus(HCV) patients;it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance.It should be considered in the nutritional care of HCV patients.
基金supported by a grant provided by Southeast University(No.9224007044)
文摘Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice,and exploring the potential molecular mechanisms.Insulin resistance in mice was induced with a high fat diet for 16 weeks.Animals were then treated with three different doses of baicalin(100,200,and 400 mg·kg^(-1)·d^(-1)for 14 weeks.Fasting blood glucose,fasting serum insulin,glucose tolerance test(GTT),insulin tolerance test(ITT),and skeletal muscle lipid deposition were measured.Additionally,the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated.Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance.Moreover,insulin resistance was significantly reversed.Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle.The properties of baicalin were mediated,at least in part,by inhibition of the AMPK/ACC pathway,a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway,a key regulator of Glycogen synthesis.These data suggest that baicalin,at dose up to 400 mg·kg^(-1)·d^(-1),is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage,through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
基金Fund Item： National Natural Science Foundation of China （K1080036）
文摘Objective： To observe the effect of acupuncture on Akt2 mRNA expression in skeletal muscle of insulin resistant rat models. Methods： Twenty-four SD rats were randomly divided into a control group, a model group and an acupuncture group. Fasting plasma glucose （FPG）, fasting insulin （FINS）, insulin sensitivity index （ISI）, C peptide （C-P）, as well as Akt2 mRNA expression in skeletal muscle of rats were detected by glucose oxidase method, ELISA and real-time PCR. Results： Compared with the control group, the level of FP~ FINS and C-P increased significantly （P〈0.01） while ISI and Akt2 mRNA expression decreased markedly in the model group （P〈0.01, P〈0.05）. In the acupuncture group, the levels of FPC FINS and C-P were much lower than in the model group （P〈0.01, P〈0.01, P〈0.05） and ISI and Akt2 mRNA expression increased markedly （P〈0.01）. Conclusion： The mechanism of acupuncture in treating insulin resistance may relate to the up-regulated of the Akt2 mRNA expression and to the improvement of the signal transduction of PI3K pathway.
基金Acknowledgements This work was supported by the Changbai Mountain Scholars Program of Jilin Province 2013046 （to Z. C.）, the Jilin Talent Development Foundation 111860000 （to Z. C.）, the National Natural Science Foundation of China Grant 31500957 （to Z. C.）, and the startup funds from Northeast Normal University 120401204 （to Z. C.）. I thank Dr. Mark J. Canet （University of Michigan） for editing this manuscript. I also thank lab members （Xinzhi Li, Wangshu Qin, Linna Jia, Sha Li, Xiaomeng Ren, Xue Dong, and Jiana Liu） at Northeast Normal University for helpful discussion. I apologize to colleagues whose relevant work could not be cited here due to space limitation.
文摘Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.
