Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The st...Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.展开更多
Menopausal metabolic syndrome(MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases(CVD) and type II diabetes mellitus(T2DM). ...Menopausal metabolic syndrome(MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases(CVD) and type II diabetes mellitus(T2DM). Erzhiwan(EZW),composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan(JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized(OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet βcells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion(GSIS), which was abolished by estrogen receptor(ER)antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.展开更多
Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients w...Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients with newly diagnosed type 2 diabetes. The purpose of this study was to investigate the effects of early insulin treatment on insulin mRNA expression and morphological alterations of β cells in a Sprague Dawley (SD) rat model of type 2 diabetes. Methods A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group of diabetic rats was then injected with protamine zinc insulin (PZI, 1-2 U·kg -1·d -1) for one week. Insulin mRNA expression, morphological features of pancreatic islets, and metabolic parameters were examined in rats using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other techniques. Results In insulin-treated diabetic rats, insulin mRNA levels prominently increased by 81.3% (P<0.05), as compared with untreated diabetic rats. Moreover, timely insulin treatment noticeably improved the insulin content of β cells, with an increase of 10.2% (P<0.05), despite a slight reduction in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA) levels, as compared to an untreated diabetic group. Conclusion Insulin treatment at the onset of T2DM effectively improves insulin synthesis, as confirmed by morphological changes to β cells in a rat model of type 2 diabetes.展开更多
AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin viaa tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated ...AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin viaa tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was conf irmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were completely abolished when mice were pretreated with NJE. Inhibition of streptozotocin-induced hyperglycemia by NJE was mediated by suppression of nuclear factor (NF)-κB activation. In addition, NJE protected against cytokine-mediated cytotoxicity. Incubation of RINm5F cells and islets with NJE resulted in a signif icant reduction in cytokine-induced NF-κB activation and downstream events, inducible nitric oxide synthase expression and nitric oxide production. The protective effect of NJE was further demonstrated by the normal insulin secretion of cytokine-treated islets in response to glucose. CONCLUSION: NJE provided resistance to pancreatic β-cell damage from cytokine or streptozotocin treatment. The β-cell protective effect of NJE is mediated by suppressing NF-κB activation.展开更多
背景:阿尔茨海默病患者存在严重的脑能量障碍,近年来基于酮体干预的脑能量拯救策略在阿尔茨海默病的治疗中越来越受到重视。目的:探讨β-羟基丁酸能否改善β淀粉样蛋白1-42(β-amyloid protein 1-42,Aβ_(1-42))诱导的小鼠海马神经元HT2...背景:阿尔茨海默病患者存在严重的脑能量障碍,近年来基于酮体干预的脑能量拯救策略在阿尔茨海默病的治疗中越来越受到重视。目的:探讨β-羟基丁酸能否改善β淀粉样蛋白1-42(β-amyloid protein 1-42,Aβ_(1-42))诱导的小鼠海马神经元HT22细胞能量障碍。方法:将HT22细胞分为4组,分别为对照组、β-羟基丁酸组、Aβ_(1-42)组、Aβ_(1-42)+β-羟基丁酸组。使用相应试剂盒检测HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位及活性氧水平。结果与结论:与对照组相比,Aβ_(1-42)组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著降低(P<0.05),活性氧水平显著升高(P<0.05)。与Aβ_(1-42)组相比,Aβ_(1-42)+β-羟基丁酸组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著升高(P<0.05),活性氧水平显著降低(P<0.05)。结果表明:β-羟基丁酸提高了线粒体生物能量功能和细胞存活率,最终改善了Aβ_(1-42)诱导的HT22细胞能量障碍。展开更多
ABC immunoperoxidase was used to test the effects of rhTGF-β1 and rhGM-CSF on receptor expressions in J6-1 and J6-2 leukemic cell lines. Computer assisted image analysis system was introduced to evaluate positive ind...ABC immunoperoxidase was used to test the effects of rhTGF-β1 and rhGM-CSF on receptor expressions in J6-1 and J6-2 leukemic cell lines. Computer assisted image analysis system was introduced to evaluate positive index of time-and dose-dependent specimens. The expression of c-kit was elevated both in positive rate and positive index by TGF-01 in both time- and dose-dependent manners. Ing/ml rhTGF-β1 simultaneously enhanced the expression of c-fms and PDGF-R which is not detected in 50 ng / ml GM-CSF treatment. Endoglin was down-regulated after TGF-β treatment and up-regulated in J6-2 cells after GM-CSF treatment, c-kit Expression was elevated by TGF-β in J6-1 cells while decreased by both in J6-2 cells.展开更多
Type 2 diabetes(T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2 DM, T2 DM ne...Type 2 diabetes(T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2 DM, T2 DM never develops unless β-cells fail to compensate insulin resistance. Recent studies have revealed that a deficit of β-cell functional mass is an essential component of the pathophysiology of T2 DM, implying that β-cell deficit is a common feature of both type 1 and type 2 diabetes. β-cell dysfunction is present at the diagnosis of T2 DM and progressively worsens with disease duration. β-cell dysfunction is associated with worseningof glycemic control and treatment failure; thus, it is important to preserve or recover β-cell functional mass in the management of T2 DM. Since β-cell regenerative capacity appears somewhat limited in humans, reducing β-cell workload appears to be the most effective way to preserve β-cell functional mass to date, underpinning the importance of lifestyle modification and weight loss for the treatment and prevention of T2 DM. This review summarizes the current knowledge on β-cell functional mass in T2 DM and discusses the treatment strategy for T2 DM.展开更多
AIM:To study the effects of Roux-en-Y gastric bypass(RYGB) on the expression of pancreatic duodenal homeobox-1(PDX-1) and pancreatic β-cell regeneration/neogenesis,and their possible mechanisms in diabetics.METHODS:T...AIM:To study the effects of Roux-en-Y gastric bypass(RYGB) on the expression of pancreatic duodenal homeobox-1(PDX-1) and pancreatic β-cell regeneration/neogenesis,and their possible mechanisms in diabetics.METHODS:Three groups of randomly selected nonobese diabetic Goto-Kakizaki(GK) rats were subjected to RYGB,sham-RYGB and sham-operation(sham-op) surgery,respectively.The rats were euthanized at postoperative 1,2,4 and 12 wk.Their pancreases were resected and analyzed using reverse transcription polymerase chain reaction to detect the mRNA of PDX-1.Anti-PDX-1 immunohistochemical(IHC) staining and Western blotting were used to detect the protein of PDX-1.Double IHC staining of anti-Brdu and-insulin was performed to detect regenerated β-cells.The index of double Brdu and insulin positive cells was calculated.RESULTS:In comparison with sham-RYGB and sham-op groups,a significant increase in the expressions of PDX-1 mRNA in RYGB group was observed at all experimental time points(1 wk:0.378 ± 0.013 vs 0.120 ± 0.010,0.100 ± 0.010,F = 727.717,P < 0.001;2 wk:0.318 ± 0.013 vs 0.110 ± 0.010,0.143 ± 0.015,F = 301.509,P < 0.001;4 wk:0.172 ± 0.011 vs 0.107 ± 0.012,0.090 ± 0.010,F = 64.297,P < 0.001;12 wk:0.140 ± 0.007 vs 0.120 ± 0.010,0.097 ± 0.015,F = 16.392,P < 0.001);PDX-1 protein in RYGB group was also increased significantly(1 wk:0.61 ± 0.01 vs 0.21 ± 0.01,0.15 ± 0.01,F = 3031.127,P < 0.001;2 wk:0.55 ± 0.00 vs 0.15 ± 0.01,0.17 ± 0.01,F = 3426.455,P < 0.001;4 wk:0.39 ± 0.01 vs 0.18 ± 0.01,0.22 ± 0.01,F = 882.909,P < 0.001;12 wk:0.41 ± 0.01 vs 0.20 ± 0.01,0.18 ± 0.01,F = 515.833,P < 0.001).PDX-1 mRNA and PDX-1 protein production showed no statistical significance between the two sham groups.Many PDX-1 positive cells could be found in the pancreatic islets of the rats in RYGB group at all time points.In addition,the percentage of Brdu-insulin double staining positive cells was higher in RYGB group than in the other two groups(1 wk:0.22 ± 0.13 vs 0.03 ± 0.06,0.03 ± 0.06,P < 0.05;2 wk:0.28 ± 0.08 vs 0.00 ± 0.00,0.03 ± 0.06,P < 0.05;4 wk:0.24 ± 0.11 vs 0.07 ± 0.06,0.00 ± 0.00,P < 0.001;12 wk:0.20 ± 0.07 vs 0.03 ± 0.06,0.00 ± 0.00,P < 0.05).CONCLUSION:RYGB can increase the expression of pancreatic PDX-1 and induce the regeneration of β-cells in GK rats.The associated regeneration of islet cells may be a possible mechanism that how RYGB could improve type 2 diabetes mellitus.展开更多
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
Objective Interferon-γ （IFN-γ） plays an important role in apoptosis and was shown to increase the riskof diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatoryproperties. In t...Objective Interferon-γ （IFN-γ） plays an important role in apoptosis and was shown to increase the riskof diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatoryproperties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in ratpancreatic β-cells.Methods The RINm5F （rat insulinoma cell line） cells exposed to IFN-γ were treated with or withoutvisfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. Theexpressions of mRNA and protein were detected by using real-time PCR and western blot analysis.Results The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of thecells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosisinduced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein,decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatinpretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic actionof visfatin was attenuated by the AMPK and ERK1/2 inhibitor.Conclusion These results suggested that visfatin protected pancreatic islet cells against IFN-γ-inducedapoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin ismediated by activation of AMPK and ERK1/2 signaling molecules.展开更多
The pancreaticβ-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus(T2DM).The persistent hyperglycemia of T2DM is often treated with...The pancreaticβ-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus(T2DM).The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections,neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas.A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreaticβ-cells that might obviate a need for exogenous insulin injections.A new study towards attaining this aim was reported by Yi et al,who have characterized a liver-derived protein,named betatrophin,capable of inducing pancreaticβ-cell proliferation in mice.Using a variety of in vitro and in vivo methods,Yi et al,have shown that betatrophin was expressed mainly in the liver and adipose tissue of mice.Exogenous expression of betatrophin in the liver led to dramatic increase in the pancreaticβ-cell mass and higher output of insulin in mice that also concomitantly elicited improved glucose tolerance.The authors discovered that betatrophin was also present in the human plasma.Surprisingly,betatrophin has been previously described by three other names,i.e.,re-feeding-induced fat and liver protein,lipasin and atypical angiopoeitin-like 8,by three independent laboratories,as nutritionally regulated liver-enriched factors that control serum triglyceride levels and lipid metabolism.Yi et al demonstration of betatrophin,as a circulating hormone that regulatesβ-cell proliferation,if successfully translated in the clinic,holds the potential to change the course of current therapies for diabetes.展开更多
In single rat pancreatic βcells, using fura-2 microfluorometry to measure [Ca2+] response upon different stimuli, the ways of calcium regulation have been studied. When the extracellular calcium concentration was 2.5...In single rat pancreatic βcells, using fura-2 microfluorometry to measure [Ca2+] response upon different stimuli, the ways of calcium regulation have been studied. When the extracellular calcium concentration was 2.5 mmol/L, either 60 mmol/L KCI, 20 mmol/L D-glucose or 0.1 mmol/L tolbutamide induced increase in [Ca2+]. Such increase in [Ca2+] was absent when the same stimuli were applied under zero extracellular calcium. These results indicate that the increase of [Ca2+] is induced by the activation of voltage-dependent calcium channels in p celis. The manifold forms of [Ca2+] change induced by glucose imply that the effects of glucose are complex. 5 mmol/L caffeine or 5 mmol/L MCh increase the [Ca2+], which is independent of the external calcium, suggesting that [Ca2+] can be regulated by Ca2+ release from not only the IP3-sensitive but also the ryanodine sensitive calcium stores in p celis. The latency of Ca responses for IP3 pathway (5 s) is faster than that for ryanodine pathway (30 s), it is展开更多
文摘Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.
基金supported by the Funds for Creative Research Groups of China,National Natural Science Foundation of China(No.81421005)the New Century Excellent Talents in University(NCET-12-0976)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Fundamental Research Funds for the Central Universities(No.ZD2014YW0030)
文摘Menopausal metabolic syndrome(MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases(CVD) and type II diabetes mellitus(T2DM). Erzhiwan(EZW),composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan(JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized(OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet βcells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion(GSIS), which was abolished by estrogen receptor(ER)antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.
文摘Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients with newly diagnosed type 2 diabetes. The purpose of this study was to investigate the effects of early insulin treatment on insulin mRNA expression and morphological alterations of β cells in a Sprague Dawley (SD) rat model of type 2 diabetes. Methods A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group of diabetic rats was then injected with protamine zinc insulin (PZI, 1-2 U·kg -1·d -1) for one week. Insulin mRNA expression, morphological features of pancreatic islets, and metabolic parameters were examined in rats using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other techniques. Results In insulin-treated diabetic rats, insulin mRNA levels prominently increased by 81.3% (P<0.05), as compared with untreated diabetic rats. Moreover, timely insulin treatment noticeably improved the insulin content of β cells, with an increase of 10.2% (P<0.05), despite a slight reduction in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA) levels, as compared to an untreated diabetic group. Conclusion Insulin treatment at the onset of T2DM effectively improves insulin synthesis, as confirmed by morphological changes to β cells in a rat model of type 2 diabetes.
基金Supported by Grant from the Ministry of Science and Technology/Korea Science and Engineering Foundation through the Diabetes Research Center at Chonbuk National University, R13-2008-005-0000-0a Research Fund of Chonbuk National University in 2009 (to Park BH)
文摘AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin viaa tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was conf irmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were completely abolished when mice were pretreated with NJE. Inhibition of streptozotocin-induced hyperglycemia by NJE was mediated by suppression of nuclear factor (NF)-κB activation. In addition, NJE protected against cytokine-mediated cytotoxicity. Incubation of RINm5F cells and islets with NJE resulted in a signif icant reduction in cytokine-induced NF-κB activation and downstream events, inducible nitric oxide synthase expression and nitric oxide production. The protective effect of NJE was further demonstrated by the normal insulin secretion of cytokine-treated islets in response to glucose. CONCLUSION: NJE provided resistance to pancreatic β-cell damage from cytokine or streptozotocin treatment. The β-cell protective effect of NJE is mediated by suppressing NF-κB activation.
文摘背景:阿尔茨海默病患者存在严重的脑能量障碍,近年来基于酮体干预的脑能量拯救策略在阿尔茨海默病的治疗中越来越受到重视。目的:探讨β-羟基丁酸能否改善β淀粉样蛋白1-42(β-amyloid protein 1-42,Aβ_(1-42))诱导的小鼠海马神经元HT22细胞能量障碍。方法:将HT22细胞分为4组,分别为对照组、β-羟基丁酸组、Aβ_(1-42)组、Aβ_(1-42)+β-羟基丁酸组。使用相应试剂盒检测HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位及活性氧水平。结果与结论:与对照组相比,Aβ_(1-42)组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著降低(P<0.05),活性氧水平显著升高(P<0.05)。与Aβ_(1-42)组相比,Aβ_(1-42)+β-羟基丁酸组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著升高(P<0.05),活性氧水平显著降低(P<0.05)。结果表明:β-羟基丁酸提高了线粒体生物能量功能和细胞存活率,最终改善了Aβ_(1-42)诱导的HT22细胞能量障碍。
基金Supported by National Natural Sciences Foundation. The abstract of this work was published in Exp Hematol (1994:22:743)
文摘ABC immunoperoxidase was used to test the effects of rhTGF-β1 and rhGM-CSF on receptor expressions in J6-1 and J6-2 leukemic cell lines. Computer assisted image analysis system was introduced to evaluate positive index of time-and dose-dependent specimens. The expression of c-kit was elevated both in positive rate and positive index by TGF-01 in both time- and dose-dependent manners. Ing/ml rhTGF-β1 simultaneously enhanced the expression of c-fms and PDGF-R which is not detected in 50 ng / ml GM-CSF treatment. Endoglin was down-regulated after TGF-β treatment and up-regulated in J6-2 cells after GM-CSF treatment, c-kit Expression was elevated by TGF-β in J6-1 cells while decreased by both in J6-2 cells.
文摘Type 2 diabetes(T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2 DM, T2 DM never develops unless β-cells fail to compensate insulin resistance. Recent studies have revealed that a deficit of β-cell functional mass is an essential component of the pathophysiology of T2 DM, implying that β-cell deficit is a common feature of both type 1 and type 2 diabetes. β-cell dysfunction is present at the diagnosis of T2 DM and progressively worsens with disease duration. β-cell dysfunction is associated with worseningof glycemic control and treatment failure; thus, it is important to preserve or recover β-cell functional mass in the management of T2 DM. Since β-cell regenerative capacity appears somewhat limited in humans, reducing β-cell workload appears to be the most effective way to preserve β-cell functional mass to date, underpinning the importance of lifestyle modification and weight loss for the treatment and prevention of T2 DM. This review summarizes the current knowledge on β-cell functional mass in T2 DM and discusses the treatment strategy for T2 DM.
基金Supported by The National Basic Research Program (973 Program),No 2007CB512705National Natural Science Foundation of China,No 30801464
文摘AIM:To study the effects of Roux-en-Y gastric bypass(RYGB) on the expression of pancreatic duodenal homeobox-1(PDX-1) and pancreatic β-cell regeneration/neogenesis,and their possible mechanisms in diabetics.METHODS:Three groups of randomly selected nonobese diabetic Goto-Kakizaki(GK) rats were subjected to RYGB,sham-RYGB and sham-operation(sham-op) surgery,respectively.The rats were euthanized at postoperative 1,2,4 and 12 wk.Their pancreases were resected and analyzed using reverse transcription polymerase chain reaction to detect the mRNA of PDX-1.Anti-PDX-1 immunohistochemical(IHC) staining and Western blotting were used to detect the protein of PDX-1.Double IHC staining of anti-Brdu and-insulin was performed to detect regenerated β-cells.The index of double Brdu and insulin positive cells was calculated.RESULTS:In comparison with sham-RYGB and sham-op groups,a significant increase in the expressions of PDX-1 mRNA in RYGB group was observed at all experimental time points(1 wk:0.378 ± 0.013 vs 0.120 ± 0.010,0.100 ± 0.010,F = 727.717,P < 0.001;2 wk:0.318 ± 0.013 vs 0.110 ± 0.010,0.143 ± 0.015,F = 301.509,P < 0.001;4 wk:0.172 ± 0.011 vs 0.107 ± 0.012,0.090 ± 0.010,F = 64.297,P < 0.001;12 wk:0.140 ± 0.007 vs 0.120 ± 0.010,0.097 ± 0.015,F = 16.392,P < 0.001);PDX-1 protein in RYGB group was also increased significantly(1 wk:0.61 ± 0.01 vs 0.21 ± 0.01,0.15 ± 0.01,F = 3031.127,P < 0.001;2 wk:0.55 ± 0.00 vs 0.15 ± 0.01,0.17 ± 0.01,F = 3426.455,P < 0.001;4 wk:0.39 ± 0.01 vs 0.18 ± 0.01,0.22 ± 0.01,F = 882.909,P < 0.001;12 wk:0.41 ± 0.01 vs 0.20 ± 0.01,0.18 ± 0.01,F = 515.833,P < 0.001).PDX-1 mRNA and PDX-1 protein production showed no statistical significance between the two sham groups.Many PDX-1 positive cells could be found in the pancreatic islets of the rats in RYGB group at all time points.In addition,the percentage of Brdu-insulin double staining positive cells was higher in RYGB group than in the other two groups(1 wk:0.22 ± 0.13 vs 0.03 ± 0.06,0.03 ± 0.06,P < 0.05;2 wk:0.28 ± 0.08 vs 0.00 ± 0.00,0.03 ± 0.06,P < 0.05;4 wk:0.24 ± 0.11 vs 0.07 ± 0.06,0.00 ± 0.00,P < 0.001;12 wk:0.20 ± 0.07 vs 0.03 ± 0.06,0.00 ± 0.00,P < 0.05).CONCLUSION:RYGB can increase the expression of pancreatic PDX-1 and induce the regeneration of β-cells in GK rats.The associated regeneration of islet cells may be a possible mechanism that how RYGB could improve type 2 diabetes mellitus.
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.
基金supported by grants from the National Natural Science Foundation of China(Nos.81100763 and 81270158)Research Fund for Doctoral Programs of Higher Education(20120001110009)
文摘Objective Interferon-γ （IFN-γ） plays an important role in apoptosis and was shown to increase the riskof diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatoryproperties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in ratpancreatic β-cells.Methods The RINm5F （rat insulinoma cell line） cells exposed to IFN-γ were treated with or withoutvisfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. Theexpressions of mRNA and protein were detected by using real-time PCR and western blot analysis.Results The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of thecells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosisinduced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein,decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatinpretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic actionof visfatin was attenuated by the AMPK and ERK1/2 inhibitor.Conclusion These results suggested that visfatin protected pancreatic islet cells against IFN-γ-inducedapoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin ismediated by activation of AMPK and ERK1/2 signaling molecules.
文摘The pancreaticβ-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus(T2DM).The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections,neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas.A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreaticβ-cells that might obviate a need for exogenous insulin injections.A new study towards attaining this aim was reported by Yi et al,who have characterized a liver-derived protein,named betatrophin,capable of inducing pancreaticβ-cell proliferation in mice.Using a variety of in vitro and in vivo methods,Yi et al,have shown that betatrophin was expressed mainly in the liver and adipose tissue of mice.Exogenous expression of betatrophin in the liver led to dramatic increase in the pancreaticβ-cell mass and higher output of insulin in mice that also concomitantly elicited improved glucose tolerance.The authors discovered that betatrophin was also present in the human plasma.Surprisingly,betatrophin has been previously described by three other names,i.e.,re-feeding-induced fat and liver protein,lipasin and atypical angiopoeitin-like 8,by three independent laboratories,as nutritionally regulated liver-enriched factors that control serum triglyceride levels and lipid metabolism.Yi et al demonstration of betatrophin,as a circulating hormone that regulatesβ-cell proliferation,if successfully translated in the clinic,holds the potential to change the course of current therapies for diabetes.
文摘In single rat pancreatic βcells, using fura-2 microfluorometry to measure [Ca2+] response upon different stimuli, the ways of calcium regulation have been studied. When the extracellular calcium concentration was 2.5 mmol/L, either 60 mmol/L KCI, 20 mmol/L D-glucose or 0.1 mmol/L tolbutamide induced increase in [Ca2+]. Such increase in [Ca2+] was absent when the same stimuli were applied under zero extracellular calcium. These results indicate that the increase of [Ca2+] is induced by the activation of voltage-dependent calcium channels in p celis. The manifold forms of [Ca2+] change induced by glucose imply that the effects of glucose are complex. 5 mmol/L caffeine or 5 mmol/L MCh increase the [Ca2+], which is independent of the external calcium, suggesting that [Ca2+] can be regulated by Ca2+ release from not only the IP3-sensitive but also the ryanodine sensitive calcium stores in p celis. The latency of Ca responses for IP3 pathway (5 s) is faster than that for ryanodine pathway (30 s), it is
