BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a redu...BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.展开更多
AIM:To investigate which obese children have an increased risk for impaired glucose tolerance(IGT),a risk factor for later diabetes.METHODS:We studied 169 European untreated obese children and adolescents with normal ...AIM:To investigate which obese children have an increased risk for impaired glucose tolerance(IGT),a risk factor for later diabetes.METHODS:We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline.Waist circumference,fasting glucose,lipids,blood pressure,pubertal stage,2 h glucose in oral glucose tolerance test(oGTT),and HbA1c were deter mined at baseline and 1 year later.RESULTS:One year after baseline,19(11.2) children demonstrated IGT,4(2.4) children had impaired fas ting glucose,no(0) child suffered from diabetes,and 146(86) children still showed normal glucose tolerance.At baseline,the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter,apart from pubertal stage.The children developing IGT entered puberty significantly more frequently(37 vs 3,P < 0.001).One year after baseline,the childr en with IGT demonstrated significantly increased waist circumference,blood pressure values,insulin and triglyceride concentrations,and insulin resistance index HOMA.The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes.CONCLUSION:During the study period of 1 year,more than 10 of the obese children with normal glucose tolerance converted to IGT.Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance,waist circumference,blood pressure,or triglyceride concen trations.展开更多
AIM: To investigate the signaling mechanism of antioxidative action by curcumin and its impact on glucose disposal. METHODS: Male C57BL/6J mice were fed with either a normal diet (n = 10) or a high fat diet (HFD) (n =...AIM: To investigate the signaling mechanism of antioxidative action by curcumin and its impact on glucose disposal. METHODS: Male C57BL/6J mice were fed with either a normal diet (n = 10) or a high fat diet (HFD) (n = 20) to induce obesity and insulin resistance. After 16 wk, 10 HFD-fed mice were further treated with daily curcumin oral gavage at the dose of 50 mg/kg body weight (BW) (HFD + curcumin group). After 15 d of the curcumin supplementation, an intraperitoneal glucose tolerance test was performed. Fasting blood samples were also collected for insulin and glucose measurements. Insulin-sensitive tissues, including muscle, adipose tissue and the liver, were isolated for the assessments of malondialdehyde (MDA), reactive oxygen species (ROS)and nuclear factor erythroid-2-related factor-2 (Nrf2) signaling. RESULTS: We show here that in a HFD mouse model, short-term curcumin gavage attenuated glucose intolerance without affecting HFD-induced BW gain. Curcumin also attenuated HFD-induced elevations of MDA and ROS in the skeletal muscle, particularly in its mitochondrial fraction, but it had no such an effect in either adipose tissue or the liver of HFD-fed mice. Correspondingly, in skeletal muscle, the levels of total or nuclear content of Nrf2, as well as its downstream target, heme oxygenase-1, were reduced by HFD-feeding. Curcumin intervention dramatically reversed these defects in Nrf2 signaling. Further analysis of the relationship of oxidative stress with glucose level by a regression analysis showed a positive and significant correlation between the area under the curve of a glucose tolerance test with MDA levels either in muscle or muscular mitochondria. CONCLUSION: These findings suggest that the shortterm treatment of curcumin in HFD-fed mice effectively ameliorates muscular oxidative stress by activating Nrf2 function that is a novel mechanism for its effect in improving glucose intolerance.展开更多
Background: The etiology of polycystic ovary syndrome (PCOS) is not completely understood;however one condition that correlates closely with the pathogenesis of PCOS is insulin resistance (IR). The objective of this s...Background: The etiology of polycystic ovary syndrome (PCOS) is not completely understood;however one condition that correlates closely with the pathogenesis of PCOS is insulin resistance (IR). The objective of this study was to determine the prevalence of insulin resistance (IR) and the association of such abnormality with potential risk factors in women with PCOS. Method: 116 women with confirmed PCOS attending a reproductive clinic at the University of Benin Teaching Hospital in Benin City were studied. IR was determined by homeostatic model assessment (HOMA) ≥ 2 and pre-diabetes by fasting plasma glucose between 110 and 125 mg/dl and/or plasma glucose value between 140 and 200 mg/dl at 2 hours during an oral glucose tolerance test (OGTT) after ingestion of 75 g oral glucose load. Results: Forty-two women were insulin resistant among the 116 women with PCOS. The prevalence of IR was 36.2% (95% CI 26.6 - 46.2). The prevalence of impaired fasting glucose (IFG) showed 1.7% (95% CI 0.97 - 2.03), impaired glucose tolerance (IGT) was 2.6% (95% CI 1.97 - 3.03) and diabetes mellitus (DM) was 1.7% (95% CI 0.97 - 2.03) in the 116 PCOS women. Of these 42 insulin resistant PCOS women, 23.8% (n = 10) were obese and 40.5% (n = 17) were overweight. Multivariate analysis revealed that total cholesterol (OR, 1.07;95% CI, 1.04 - 1.10), triglycerides (OR, 1.08;95% CI, 1.04 - 1.13) and LDL-cholesterol (OR, 1.08;95% CI, 1.04 - 1.12) were statistically significant independent risk factors for IR. Conclusion: The prevalence of IR was high in women with PCOS, and there was a significant association between IR, obesity, and dyslipidemia. However, the prevalence rates of impaired glucose tolerance and DM were low in women with PCOS compared to other studies. Since women with PCOS are at risk of IR and dyslipidemia, early screening, detection, intervention, and lifestyle modification would ameliorate the financial burden of DM and cardiovascular disease (CVD).展开更多
基金Supported by the National Natural Science Foundation of China,No.31771284Basic Research Project of Yantai Science and Technology Innovation and Development Plan,No.2022JCYJ026+1 种基金Natural Science Foundation of Shandong province,No.ZR202111250163Yantai Science and Technology Plan Project,No.2022YD062.
文摘BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.
基金Supported by the Grants from the German ‘Competence Net Obesity’,which is supported by the German Federal Ministry of Education and Research,No. 01 GI0839the University of Witten/Herdecke and the German Ministry of Education and Research (Bundesministerium für Bildung und ForschungNational Genome Research Network,NGFNplus,No. 01GS0820)
文摘AIM:To investigate which obese children have an increased risk for impaired glucose tolerance(IGT),a risk factor for later diabetes.METHODS:We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline.Waist circumference,fasting glucose,lipids,blood pressure,pubertal stage,2 h glucose in oral glucose tolerance test(oGTT),and HbA1c were deter mined at baseline and 1 year later.RESULTS:One year after baseline,19(11.2) children demonstrated IGT,4(2.4) children had impaired fas ting glucose,no(0) child suffered from diabetes,and 146(86) children still showed normal glucose tolerance.At baseline,the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter,apart from pubertal stage.The children developing IGT entered puberty significantly more frequently(37 vs 3,P < 0.001).One year after baseline,the childr en with IGT demonstrated significantly increased waist circumference,blood pressure values,insulin and triglyceride concentrations,and insulin resistance index HOMA.The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes.CONCLUSION:During the study period of 1 year,more than 10 of the obese children with normal glucose tolerance converted to IGT.Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance,waist circumference,blood pressure,or triglyceride concen trations.
基金Supported by A National Natural Science Foundation of China Grant, No. 81072300 to Jin TR andYu ZW
文摘AIM: To investigate the signaling mechanism of antioxidative action by curcumin and its impact on glucose disposal. METHODS: Male C57BL/6J mice were fed with either a normal diet (n = 10) or a high fat diet (HFD) (n = 20) to induce obesity and insulin resistance. After 16 wk, 10 HFD-fed mice were further treated with daily curcumin oral gavage at the dose of 50 mg/kg body weight (BW) (HFD + curcumin group). After 15 d of the curcumin supplementation, an intraperitoneal glucose tolerance test was performed. Fasting blood samples were also collected for insulin and glucose measurements. Insulin-sensitive tissues, including muscle, adipose tissue and the liver, were isolated for the assessments of malondialdehyde (MDA), reactive oxygen species (ROS)and nuclear factor erythroid-2-related factor-2 (Nrf2) signaling. RESULTS: We show here that in a HFD mouse model, short-term curcumin gavage attenuated glucose intolerance without affecting HFD-induced BW gain. Curcumin also attenuated HFD-induced elevations of MDA and ROS in the skeletal muscle, particularly in its mitochondrial fraction, but it had no such an effect in either adipose tissue or the liver of HFD-fed mice. Correspondingly, in skeletal muscle, the levels of total or nuclear content of Nrf2, as well as its downstream target, heme oxygenase-1, were reduced by HFD-feeding. Curcumin intervention dramatically reversed these defects in Nrf2 signaling. Further analysis of the relationship of oxidative stress with glucose level by a regression analysis showed a positive and significant correlation between the area under the curve of a glucose tolerance test with MDA levels either in muscle or muscular mitochondria. CONCLUSION: These findings suggest that the shortterm treatment of curcumin in HFD-fed mice effectively ameliorates muscular oxidative stress by activating Nrf2 function that is a novel mechanism for its effect in improving glucose intolerance.
文摘Background: The etiology of polycystic ovary syndrome (PCOS) is not completely understood;however one condition that correlates closely with the pathogenesis of PCOS is insulin resistance (IR). The objective of this study was to determine the prevalence of insulin resistance (IR) and the association of such abnormality with potential risk factors in women with PCOS. Method: 116 women with confirmed PCOS attending a reproductive clinic at the University of Benin Teaching Hospital in Benin City were studied. IR was determined by homeostatic model assessment (HOMA) ≥ 2 and pre-diabetes by fasting plasma glucose between 110 and 125 mg/dl and/or plasma glucose value between 140 and 200 mg/dl at 2 hours during an oral glucose tolerance test (OGTT) after ingestion of 75 g oral glucose load. Results: Forty-two women were insulin resistant among the 116 women with PCOS. The prevalence of IR was 36.2% (95% CI 26.6 - 46.2). The prevalence of impaired fasting glucose (IFG) showed 1.7% (95% CI 0.97 - 2.03), impaired glucose tolerance (IGT) was 2.6% (95% CI 1.97 - 3.03) and diabetes mellitus (DM) was 1.7% (95% CI 0.97 - 2.03) in the 116 PCOS women. Of these 42 insulin resistant PCOS women, 23.8% (n = 10) were obese and 40.5% (n = 17) were overweight. Multivariate analysis revealed that total cholesterol (OR, 1.07;95% CI, 1.04 - 1.10), triglycerides (OR, 1.08;95% CI, 1.04 - 1.13) and LDL-cholesterol (OR, 1.08;95% CI, 1.04 - 1.12) were statistically significant independent risk factors for IR. Conclusion: The prevalence of IR was high in women with PCOS, and there was a significant association between IR, obesity, and dyslipidemia. However, the prevalence rates of impaired glucose tolerance and DM were low in women with PCOS compared to other studies. Since women with PCOS are at risk of IR and dyslipidemia, early screening, detection, intervention, and lifestyle modification would ameliorate the financial burden of DM and cardiovascular disease (CVD).
