Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glu...Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de- crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy- ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance.展开更多
In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions e...In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions enumerated therein.The study has provided important evidence to improve maternal and child health in the Asian population.The methods,however,appear to have considerable limi-tations,wherein the time point of diagnosis of GDM,severity of GDM,selection bias,compliance to therapy,important maternal covariates,observable microvascular abnormalities and the confounding effect of added insulin have not been considered.We have provided suggestions to improve the external validity of the study,including the use of Equator Network reporting guidelines and inclusion of overweight and obese patients in future studies.展开更多
This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and ...This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and efficacy,this Meta-Analysis is inconclusive.展开更多
The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a conse...The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a consequence of LC is referred to as HD.In patients with LC,the prevalence rates of HD have been reported to vary from 21%to 57%.The pathophysiological basis of HD seems to involve insulin resistance(IR)and pancreaticβ-cell dysfunction.The neurohormonal changes,endotoxemia,and chronic inflammation of LC initially create IR;however,the toxic effects eventually lead toβ-cell dysfunction,which marks the transition from impaired glucose tolerance to HD.In addition,a number of factors,including sarcopenia,sarcopenic obesity,gut dysbiosis,and hyperammonemia,have recently been linked to impaired glucose metabolism in LC.DM is associated with complications and poor outcomes in patients with LC,although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research.In fact,there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC.Currently,T2DM and HD are being treated in a similar manner although no standardized guidelines are available.The different pathophysiological basis of HD may have an impact on treatment options.This review article discusses the existence of HD as a distinct entity with high prevalence rates,a strong pathophysiological basis,clinical and therapeutic implications,as well as widespread skepticism and knowledge gaps.展开更多
BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Unders...BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.展开更多
Gestational mellitus diabetes (GDM) is a highly prevalent metabolic disorder among pregnant women nowadays. It is defined as any level of glucose intolerance, appearing or first being recognized during pregnancy. It i...Gestational mellitus diabetes (GDM) is a highly prevalent metabolic disorder among pregnant women nowadays. It is defined as any level of glucose intolerance, appearing or first being recognized during pregnancy. It is essential to diagnose and treat GDM early, in order to reduce or avoid complications for mother and fetus. Recently, new guidelines have changed the diagnosis criteria, and it is expected that the prevalence of GDM will increase by approximately 18%. A relevant goal of these new definitions is to provide a better care for pregnant women, in an attempt to reduce fetal and maternal complications. These new criteria will also increase the impact on costs of the health care system. Treatment must be individualized for best results, including a specific diet, physical activity and the use of medications. Metformin and Insulin use are analyzed in detail, in face of new evidences regarding their safety and efficacy during pregnancy.展开更多
Background: Although recent meta-analyses indicates a consistent significant inverse relation of serum 25 (OH) D and the prevalence of gestational diabetes mellitus (GDM), the mechanism is unclear and conflicting opin...Background: Although recent meta-analyses indicates a consistent significant inverse relation of serum 25 (OH) D and the prevalence of gestational diabetes mellitus (GDM), the mechanism is unclear and conflicting opinions continue to be reported. Objectives: The objectives are: 1) comparison of vitamin D status in diabetic and non-diabetic pregnant women;2) trying to determine the level of vitamin D associated with GDM, and its sensitivity and specificity;3) determination of the relation of hypovitaminosis D with insulin resistance. Subjects and Methods: One hundred consecutive pregnant women (<28 weeks gestational period) from the attendants of the out-patient clinic at our hospital were diagnosed for GDM by glucose tolerance test (GTT) (75 g 2 h). Among them, 40 patients met the inclusion criteria for this study (group I). As a comparative group, another 40 pregnant ladies were included, 20 of them (group II) had pre-gestational type II DM, and the other 20 (group III) had normal glucose tolerance (NGT) as a control. For all the participants, we estimated fasting blood glucose, fasting serum insulin, homeostasis model assessment of (HOMA-IR and HOMA-B), quantitative insulin sensitivity check index (QUICKI), and serum 25-OH vit D. The ROC curve analysis was used to determine the optimal threshold value of vit D in relation to DM. Results: Compared to the control group, the diabetic patients showed a statistically significant increase in the levels of fasting glucose, 1-hour postprandial glucose, 2-hour post prandial glucose, fasting insulin, and HOMA-IR, (P=0.000 for all). None of the diabetic patients showed optimal vit D level. Vit D insuficiency (10 - 29 ng/ml) was found in 32.5% of patients in group I, 55% in group II, and 50% in group III. Vit D deficiency (<10 ng/ml) was found in 67.5% of patients in group I, 45% in group II, and 0% in group III. Significant negative correlation was found for vit D with fasting insulin and FBS. The AUC for 25 OH vit D was 97%, CI was 95% and p-value was 0.0001. The sensitivity, specificity, and positive and negative predictive values of 25 OH vit D in GDM versus control persons were 97%, 90%, 95.1%, 94.7% respectively at a cut-off level <22 ng/ml. Conclusions: Although it might seem premature to draw a sharp relation between hypovitaminosis D and GDM, this study showed the importance of vit D in GDM, the need for supplementation below 22 ng/ml, and the role of hypovitaminosis D in increasing insulin resistance. Further randomized studies with vit D supplementation are recommended.展开更多
Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring...Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.展开更多
基金supported by the Talent Foundation of the Affiliated Hospital of Guangxi Medical College in China,No.08026Youth Researcher Foundation of Guangxi Medical College in China,No.08012Scientific Research Foundation from Science and Technology Bureau of Shanghai City,No.074119048
文摘Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose me- tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de- crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy- ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance.
文摘In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions enumerated therein.The study has provided important evidence to improve maternal and child health in the Asian population.The methods,however,appear to have considerable limi-tations,wherein the time point of diagnosis of GDM,severity of GDM,selection bias,compliance to therapy,important maternal covariates,observable microvascular abnormalities and the confounding effect of added insulin have not been considered.We have provided suggestions to improve the external validity of the study,including the use of Equator Network reporting guidelines and inclusion of overweight and obese patients in future studies.
文摘This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and efficacy,this Meta-Analysis is inconclusive.
文摘The diabetogenic potential of liver cirrhosis(LC)has been known for a long time,and the name"hepatogenous diabetes"(HD)was coined in 1906 to define the condition.Diabetes mellitus(DM)that develops as a consequence of LC is referred to as HD.In patients with LC,the prevalence rates of HD have been reported to vary from 21%to 57%.The pathophysiological basis of HD seems to involve insulin resistance(IR)and pancreaticβ-cell dysfunction.The neurohormonal changes,endotoxemia,and chronic inflammation of LC initially create IR;however,the toxic effects eventually lead toβ-cell dysfunction,which marks the transition from impaired glucose tolerance to HD.In addition,a number of factors,including sarcopenia,sarcopenic obesity,gut dysbiosis,and hyperammonemia,have recently been linked to impaired glucose metabolism in LC.DM is associated with complications and poor outcomes in patients with LC,although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research.In fact,there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC.Currently,T2DM and HD are being treated in a similar manner although no standardized guidelines are available.The different pathophysiological basis of HD may have an impact on treatment options.This review article discusses the existence of HD as a distinct entity with high prevalence rates,a strong pathophysiological basis,clinical and therapeutic implications,as well as widespread skepticism and knowledge gaps.
基金Supported by the Swiss National Science Foundation,No.P2SKP3_158649,No.P3400PB_171581,and No.P3P3PB_171582(to Bluemel S)NIH grants(in part),No.R01 AA24726,No.U01 AA026939,and services provided by P30 DK120515(to Schnabl B).
文摘BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.
文摘Gestational mellitus diabetes (GDM) is a highly prevalent metabolic disorder among pregnant women nowadays. It is defined as any level of glucose intolerance, appearing or first being recognized during pregnancy. It is essential to diagnose and treat GDM early, in order to reduce or avoid complications for mother and fetus. Recently, new guidelines have changed the diagnosis criteria, and it is expected that the prevalence of GDM will increase by approximately 18%. A relevant goal of these new definitions is to provide a better care for pregnant women, in an attempt to reduce fetal and maternal complications. These new criteria will also increase the impact on costs of the health care system. Treatment must be individualized for best results, including a specific diet, physical activity and the use of medications. Metformin and Insulin use are analyzed in detail, in face of new evidences regarding their safety and efficacy during pregnancy.
文摘Background: Although recent meta-analyses indicates a consistent significant inverse relation of serum 25 (OH) D and the prevalence of gestational diabetes mellitus (GDM), the mechanism is unclear and conflicting opinions continue to be reported. Objectives: The objectives are: 1) comparison of vitamin D status in diabetic and non-diabetic pregnant women;2) trying to determine the level of vitamin D associated with GDM, and its sensitivity and specificity;3) determination of the relation of hypovitaminosis D with insulin resistance. Subjects and Methods: One hundred consecutive pregnant women (<28 weeks gestational period) from the attendants of the out-patient clinic at our hospital were diagnosed for GDM by glucose tolerance test (GTT) (75 g 2 h). Among them, 40 patients met the inclusion criteria for this study (group I). As a comparative group, another 40 pregnant ladies were included, 20 of them (group II) had pre-gestational type II DM, and the other 20 (group III) had normal glucose tolerance (NGT) as a control. For all the participants, we estimated fasting blood glucose, fasting serum insulin, homeostasis model assessment of (HOMA-IR and HOMA-B), quantitative insulin sensitivity check index (QUICKI), and serum 25-OH vit D. The ROC curve analysis was used to determine the optimal threshold value of vit D in relation to DM. Results: Compared to the control group, the diabetic patients showed a statistically significant increase in the levels of fasting glucose, 1-hour postprandial glucose, 2-hour post prandial glucose, fasting insulin, and HOMA-IR, (P=0.000 for all). None of the diabetic patients showed optimal vit D level. Vit D insuficiency (10 - 29 ng/ml) was found in 32.5% of patients in group I, 55% in group II, and 50% in group III. Vit D deficiency (<10 ng/ml) was found in 67.5% of patients in group I, 45% in group II, and 0% in group III. Significant negative correlation was found for vit D with fasting insulin and FBS. The AUC for 25 OH vit D was 97%, CI was 95% and p-value was 0.0001. The sensitivity, specificity, and positive and negative predictive values of 25 OH vit D in GDM versus control persons were 97%, 90%, 95.1%, 94.7% respectively at a cut-off level <22 ng/ml. Conclusions: Although it might seem premature to draw a sharp relation between hypovitaminosis D and GDM, this study showed the importance of vit D in GDM, the need for supplementation below 22 ng/ml, and the role of hypovitaminosis D in increasing insulin resistance. Further randomized studies with vit D supplementation are recommended.
文摘Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.