AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether th...AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.展开更多
Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms...Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms associated with cognitive function in obese youth. The objective of the present study was to assess the associations among cognitive functioning and insulin regulation in a sample of obese youth. Methods: The sample consisted of 30 obese, non-diabetic youth (BMI > 95th percentile) ages 6-16 years (mean age = 12.60 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and Wide Range Assessment of Memory and Learning (WRAML-2). Results: Verbal memory, attention/concentration, and intelligence scores were similar across obese youth with elevated insulin levels and normal insulin levels. Obese youth with elevated insulin levels had lower scores in visual memory, with a medium effect (effect size = 0.51). Fasting insulin levels were not associated with any of the four cognitive domains in the multiple linear regression analysis (P > 0.05). Conclusions: These data provide preliminary evidence that visual memory may be impacted in obese youth with insulin resistance. Longitudinal studies examining insulin regulation, cognitive functioning, and weight status over time are needed.展开更多
β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line ora...β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.展开更多
Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insuli...Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insulin preparations has undergone nearly 100 years of history,from early animal insulin extraction to modern synthetic insulin and insulin analogs,which have greatly advanced the treatment of diabetes.The insulin receptor has a wide distribution in the body,and its activation leads to intracellular signaling mainly through two pathways,PI3K/Akt and Ras/MAPK.Clinically,insulin is crucial in the treatment and management of diabetes and its complications,especially in the cases where oral medications fail to control blood glucose.The role of insulin is not limited to the regulation of blood glucose but has a wide range of functions throughout the body,such as regulation of mitochondrial function and metabolism,the promotion of protein synthesis,adipogenesis,and cellular proliferation.However,insulin overdose may lead to severe hypoglycemia,which,if left untreated,poses the risk of irreversible neurological damage or even fatality.In this paper,we review the history of the development of insulin preparations,the molecular structure of insulin,the biological processes initiated by insulin and insulin deficiency/resistance.The overview of side effects from insulin is also included in this review.We assume that future research could focus on refining insulin analogs for greater therapeutic precision,minimizing side effects,and extending benefits beyond glycemic control.Exploring insulin’s additional effects may unlock potential applications in treating multiple diseases.展开更多
Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is ...Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.展开更多
目的观察达格列净联合二甲双胍治疗超重2型糖尿病患者的临床疗效。方法选取超重2型糖尿病患者60例,以随机数字表法分为两组(对照组、观察组),每组30例。对照组接受二甲双胍治疗,观察组接受达格列净联合二甲双胍治疗。比较两组治疗效果,...目的观察达格列净联合二甲双胍治疗超重2型糖尿病患者的临床疗效。方法选取超重2型糖尿病患者60例,以随机数字表法分为两组(对照组、观察组),每组30例。对照组接受二甲双胍治疗,观察组接受达格列净联合二甲双胍治疗。比较两组治疗效果,治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)],治疗前后血脂[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]水平,治疗前后胰岛素[胰岛素β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)]水平及体格指标[体质量指数(BMI)、腰围],治疗前后肝肾功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(Cr)、尿素氮(BUN)、肾小球滤过率(GFR)、血尿酸(UA)],不良反应发生率。结果治疗6个月后,观察组总有效率为93.33%,显著高于对照组的63.33%(P<0.05)。治疗后,观察组HbA1c(6.03±0.25)%、FPG(6.93±0.91)mmol/L、2 h PG(8.18±1.12)mmol/L均显著低于对照组的(8.51±0.67)%、(8.74±2.17)mmol/L、(10.15±1.19)mmol/L(P<0.05)。治疗后,与对照组的(5.41±0.52)、(2.34±0.29)、(2.47±0.13)、(0.93±0.11)mmol/L比较,观察组TC(4.29±0.44)mmol/L、TG(1.62±0.15)mmol/L、LDL-C(2.08±0.08)mmol/L更低,HDL-C(1.44±0.15)mmol/L更高(P<0.05)。治疗后,观察组HOMA-β(10.42±1.48)高于对照组的(8.41±1.27),HOMA-IR(1.97±0.24)、BMI(26.12±1.22)kg/m^(2)、腰围(77.96±2.85)cm均低于对照组的(3.14±0.35)、(27.83±1.32)kg/m^(2)、(84.84±3.05)cm(P<0.05)。治疗后,观察组ALT(38.55±2.34)U/L、AST(35.58±2.11)U/L相比对照组的(42.49±3.11)、(39.55±2.66)U/L均更低(P<0.05);两组Cr、BUN、GFR、UA比较无差异(P>0.05)。对照组发生不良反应共11例(36.67%),观察组发生不良反应共12例(40.00%),两组不良反应发生率比较无差异(P>0.05)。结论超重2型糖尿病患者接受达格列净联合二甲双胍治疗安全有效,可有效改善患者血糖、血脂、胰岛素、体格指标以及肝功能,并不会对肾功能造成损伤。展开更多
Type 2 diabetes is a complicated metabolic disorder with both short- and long-term undesirable complications. In recent years, there has been growing evidence that functional foods and their bioactive compounds, due t...Type 2 diabetes is a complicated metabolic disorder with both short- and long-term undesirable complications. In recent years, there has been growing evidence that functional foods and their bioactive compounds, due to their biological properties, may be used as complementary treatment for type 2 diabetes mellitus. In this review, we have highlighted various functional foods as missing part of medical nutrition therapy in diabetic patients. Several in vitro, animal models and some human studies, have demonstrated that functional foods and nutraceuticals may improve postprandial hyperglycemia and adipose tissue metabolism modulatecarbohydrate and lipid metabolism. Functional foods may also improve dyslipidemia and insulin resistance, and attenuate oxidative stress and inflammatory processes and subsequently could prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. In conclusion available data indicate that a functional foods-based diet may be a novel and comprehensive dietary approach for management of type 2 diabetes.展开更多
糖尿病是一种常见的代谢性疾病,其病因和病程主要与胰岛素分泌不足和胰岛素抵抗密切相关。代谢重编程是细胞在病理或应激条件下重塑代谢途径以适应能量与生物合成需求的过程。研究表明,在糖尿病中,代谢重编程可通过影响线粒体功能、糖...糖尿病是一种常见的代谢性疾病,其病因和病程主要与胰岛素分泌不足和胰岛素抵抗密切相关。代谢重编程是细胞在病理或应激条件下重塑代谢途径以适应能量与生物合成需求的过程。研究表明,在糖尿病中,代谢重编程可通过影响线粒体功能、糖酵解和脂代谢等影响胰岛素敏感性和胰岛β细胞功能。本文系统综述了代谢重编程在糖尿病发生、发展过程中的变化特征和作用机制,并重点介绍了胰岛素信号通路和单磷酸腺苷活化蛋白激酶(adenosine 5′-monophosphate-activated protein kinase,AMPK)信号通路在调控糖、脂代谢中的作用,旨在为了解糖尿病发病机制及其寻找防治、靶向干预策略提供新思路。展开更多
AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were...AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated. RESULTS: Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression. CONCLUSION: Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.展开更多
Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and...Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and insulin （IR） in the development of AD are still controversial. This study was designed to evaluate or IR influenced the cognitive functions of older cohort. Methods The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose （FBG） and fasting insulin （FINS） were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. Results In our study, there were 180 participants with HI and 148 without HI, and 192 with iR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model I adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. Conclusion HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.展开更多
基金Supported by the Beijing Natural Science Foundation(No.7131007)National Basic Research Program of China(973 ProgramNo.2007CB512201)
文摘AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.
文摘Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms associated with cognitive function in obese youth. The objective of the present study was to assess the associations among cognitive functioning and insulin regulation in a sample of obese youth. Methods: The sample consisted of 30 obese, non-diabetic youth (BMI > 95th percentile) ages 6-16 years (mean age = 12.60 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and Wide Range Assessment of Memory and Learning (WRAML-2). Results: Verbal memory, attention/concentration, and intelligence scores were similar across obese youth with elevated insulin levels and normal insulin levels. Obese youth with elevated insulin levels had lower scores in visual memory, with a medium effect (effect size = 0.51). Fasting insulin levels were not associated with any of the four cognitive domains in the multiple linear regression analysis (P > 0.05). Conclusions: These data provide preliminary evidence that visual memory may be impacted in obese youth with insulin resistance. Longitudinal studies examining insulin regulation, cognitive functioning, and weight status over time are needed.
文摘β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.
基金supported by grants from National Natural Science Foundation of China(Grant No.82301577).
文摘Insulin is a peptide hormone secreted by pancreaticβ-cells,which plays a key role in regulating glucose metabolism and is the only hormone in the body capable of lowering blood glucose level.The development of insulin preparations has undergone nearly 100 years of history,from early animal insulin extraction to modern synthetic insulin and insulin analogs,which have greatly advanced the treatment of diabetes.The insulin receptor has a wide distribution in the body,and its activation leads to intracellular signaling mainly through two pathways,PI3K/Akt and Ras/MAPK.Clinically,insulin is crucial in the treatment and management of diabetes and its complications,especially in the cases where oral medications fail to control blood glucose.The role of insulin is not limited to the regulation of blood glucose but has a wide range of functions throughout the body,such as regulation of mitochondrial function and metabolism,the promotion of protein synthesis,adipogenesis,and cellular proliferation.However,insulin overdose may lead to severe hypoglycemia,which,if left untreated,poses the risk of irreversible neurological damage or even fatality.In this paper,we review the history of the development of insulin preparations,the molecular structure of insulin,the biological processes initiated by insulin and insulin deficiency/resistance.The overview of side effects from insulin is also included in this review.We assume that future research could focus on refining insulin analogs for greater therapeutic precision,minimizing side effects,and extending benefits beyond glycemic control.Exploring insulin’s additional effects may unlock potential applications in treating multiple diseases.
文摘Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.
文摘目的观察达格列净联合二甲双胍治疗超重2型糖尿病患者的临床疗效。方法选取超重2型糖尿病患者60例,以随机数字表法分为两组(对照组、观察组),每组30例。对照组接受二甲双胍治疗,观察组接受达格列净联合二甲双胍治疗。比较两组治疗效果,治疗前后血糖指标[空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)],治疗前后血脂[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]水平,治疗前后胰岛素[胰岛素β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)]水平及体格指标[体质量指数(BMI)、腰围],治疗前后肝肾功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(Cr)、尿素氮(BUN)、肾小球滤过率(GFR)、血尿酸(UA)],不良反应发生率。结果治疗6个月后,观察组总有效率为93.33%,显著高于对照组的63.33%(P<0.05)。治疗后,观察组HbA1c(6.03±0.25)%、FPG(6.93±0.91)mmol/L、2 h PG(8.18±1.12)mmol/L均显著低于对照组的(8.51±0.67)%、(8.74±2.17)mmol/L、(10.15±1.19)mmol/L(P<0.05)。治疗后,与对照组的(5.41±0.52)、(2.34±0.29)、(2.47±0.13)、(0.93±0.11)mmol/L比较,观察组TC(4.29±0.44)mmol/L、TG(1.62±0.15)mmol/L、LDL-C(2.08±0.08)mmol/L更低,HDL-C(1.44±0.15)mmol/L更高(P<0.05)。治疗后,观察组HOMA-β(10.42±1.48)高于对照组的(8.41±1.27),HOMA-IR(1.97±0.24)、BMI(26.12±1.22)kg/m^(2)、腰围(77.96±2.85)cm均低于对照组的(3.14±0.35)、(27.83±1.32)kg/m^(2)、(84.84±3.05)cm(P<0.05)。治疗后,观察组ALT(38.55±2.34)U/L、AST(35.58±2.11)U/L相比对照组的(42.49±3.11)、(39.55±2.66)U/L均更低(P<0.05);两组Cr、BUN、GFR、UA比较无差异(P>0.05)。对照组发生不良反应共11例(36.67%),观察组发生不良反应共12例(40.00%),两组不良反应发生率比较无差异(P>0.05)。结论超重2型糖尿病患者接受达格列净联合二甲双胍治疗安全有效,可有效改善患者血糖、血脂、胰岛素、体格指标以及肝功能,并不会对肾功能造成损伤。
基金Supported by Research Institute of Endocrine Sciences,Shahid Beheshti University of Medical Sciences,Tehran,Iran
文摘Type 2 diabetes is a complicated metabolic disorder with both short- and long-term undesirable complications. In recent years, there has been growing evidence that functional foods and their bioactive compounds, due to their biological properties, may be used as complementary treatment for type 2 diabetes mellitus. In this review, we have highlighted various functional foods as missing part of medical nutrition therapy in diabetic patients. Several in vitro, animal models and some human studies, have demonstrated that functional foods and nutraceuticals may improve postprandial hyperglycemia and adipose tissue metabolism modulatecarbohydrate and lipid metabolism. Functional foods may also improve dyslipidemia and insulin resistance, and attenuate oxidative stress and inflammatory processes and subsequently could prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. In conclusion available data indicate that a functional foods-based diet may be a novel and comprehensive dietary approach for management of type 2 diabetes.
文摘糖尿病是一种常见的代谢性疾病,其病因和病程主要与胰岛素分泌不足和胰岛素抵抗密切相关。代谢重编程是细胞在病理或应激条件下重塑代谢途径以适应能量与生物合成需求的过程。研究表明,在糖尿病中,代谢重编程可通过影响线粒体功能、糖酵解和脂代谢等影响胰岛素敏感性和胰岛β细胞功能。本文系统综述了代谢重编程在糖尿病发生、发展过程中的变化特征和作用机制,并重点介绍了胰岛素信号通路和单磷酸腺苷活化蛋白激酶(adenosine 5′-monophosphate-activated protein kinase,AMPK)信号通路在调控糖、脂代谢中的作用,旨在为了解糖尿病发病机制及其寻找防治、靶向干预策略提供新思路。
基金Supported by The National Natural Science Foundation of China, No. 30971354The International Cooperation Project of Jiangsu Province Department of Health, No. SBZ201100103The Graduate Innovation Foundation of Jiangsu Province, China,No. CXZZ11_0704
文摘AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated. RESULTS: Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression. CONCLUSION: Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.
基金supported by the Medical College Natural Science Foundation of Shanghai Jiao Tong University (09XJ21028)the Shanghai Jiaotong University Interdisciplinary Study Foundation Medicine and Engineer
文摘Objective decline of resistance whether H Type 2 diabetes has been recently recognized as an important risk factor for cognitive patients with Alzheimer＇s disease （AD）. But the roles of hyperinsulinemia （HI） and insulin （IR） in the development of AD are still controversial. This study was designed to evaluate or IR influenced the cognitive functions of older cohort. Methods The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose （FBG） and fasting insulin （FINS） were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. Results In our study, there were 180 participants with HI and 148 without HI, and 192 with iR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model I adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. Conclusion HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.
