【摘要】 目的 探讨血浆内脏脂肪素(visfatin)与2型糖尿病的关系。方法 2007年7月—9月选取2型糖尿病患者和正常对照组各40例。根据体重指数再分为超重肥胖组和非超重肥胖组。检测visfatin水平、空腹血糖、空腹胰岛素、血脂、血压等,计算腰臀比、体重指数、稳态模型胰岛素抵抗指数homeostasis model assessment of insulin resistance,HOMAIR)及胰岛素分泌功能(HOMAβ)。结果 2型糖尿病组血浆visfatin水平显著低于正常对照组(Plt;0.05)。多元逐步相关分析表明,在肥胖的2型糖尿病个体中visfatin与高密度脂蛋白胆固醇、空腹血糖、体重指数呈负相关。二分类Logstic回归分析显示血浆visfatin及胰岛素抵抗指数与2型糖尿病的发生显著相关,回归方程式为Y=7.681+2.417 ln HOMAIR-2.549 visfatin。结论 visfatin的变化可能对2型糖尿病的发生、发展具有一定作用。
ObjectiveTo observe expre with ssions of insulin receptor substrate 1(IRS-1) and ubiquitin-protein in skeletal muscle of non-obese rats with type 2 diabetes mellitus following gastric bypass operation (GBP), and to investigate possible mechanism of GBP in improving insulin resistance. MethodsMale GK rats were randomly divided into diabetic operation group (DO group), diabetic sham operation group (DSO group), and diabetic control group (DC group), 8 rats in each group; besides 8 male Wistar rats were served as normal control group (NC group). Fasting body weight (FBW), fasting plasma glucose (FPG), and fasting insulin (FINS) were measured respectively before operation and on week 1, 2, 4 and 8 after operation. Homeostasis model-insulin resistant (HOMA-IR) index was calculated respectively before operation and on week 8 after operation. The expressions of IRS-1 protein and ubiquitin-protein in skeletal muscle were detected by using Western blot method on week 8 after operation. Results① Compared with the preoperative levels, the FBWs on week 1, 2, and 4 after operation markedly decreased (P < 0.05), but it recovered to the preoperative level on week 8 after operation (P > 0.05) in the DO group; which in the DSO group decreased on week 1 after operation (P < 0.05) and then increased on week 4 after operation (P < 0.05); which in the DC group or the NC group increased continuously and had a significant difference on week 8 after operation (P < 0.05).② The FPGs in the DO, DSO and DC groups were significantly higher than those of the NC group before operation (P < 0.05), which in the DO group decreased from (9.10±0.98) mmoL/L before operation to (5.70±0.91) mmol/L on week 8 after operation (P < 0.05) and were significantly lower than those of the DSO group or the DC group on week 2, 4, and 8 after operation (P < 0.05); which in the DC group, DSO group and NC group had no obviously changes between before and after operations (P > 0.05). ③ The FINS had no significant differences among these four groups before operation (P > 0.05), which in the DO group obviously increased[(9.64±1.59) mU/L] on week 2 after operation (P < 0.05) and then obviously decreased[(6.58±1.05) mU/L] on week 8 after operation (P < 0.05) and significantly lower than those of the DSO group or the DC group on week 8 after operation (P < 0.05), while which had no significant difference between before and after operations in the DSO group, the DC group, or the NC group (P > 0.05). ④ The HOMA-IR index in the DO, DSO or DC group was significantly higher than that of the NC group before operation (P < 0.05), which in the DO group markedly decreased from 3.18±0.50 before operation to 1.96±0.63 on week 8 after operation (P < 0.05) and significantly lower than that of the DSO group or the DC group on week 8 after operation (P < 0.05), while which had no significant difference between before and after operations in the DSO group, the DC group, or the NC group (P > 0.05). ⑤ The expression of IRS-1 protein in the DO group was significantly higher than that in the DSO group (P < 0.05) or the DC group (P < 0.05) on week 8 after operation. While there was no significant difference between the DSO and the DC group after operation (P > 0.05). ⑥ Compared with the NC group, the expression of ubiquitin-protein was significantly increased in the DO group, the DSO group, or the DC group (P < 0.05). Compared with the DSO group or the DC group, the expression of ubiquitin-protein was significantly decreased in the DO group on week 8 after operation (P < 0.05), especially it was most obvious near the molecular weight of 180×103. While there was no significant difference between the DSO group and the DC group after operation (P > 0.05). ConclusionsExpression of IRS-1 protein in skeletal muscle insulin signaling pathway in type 2 diabetes mellitus rats following GBP is increased, it might be associated with decreasing ubiquitin-protein level in skeletal muscle, thus reduces the IRS-1 ubiquitin-degradation, increase insulin sensitivity, and improve insulin resistance of skeletal muscle.
Objective To summarize the relationship of diabetes and its complications with microRNA. Methods Domestic and international researches were collected by searching to summarize the role of microRNA in diabetes and its complications. Results MicroRNA could affect the secretion of insulin and interfer metabolism of gulcose in fat cells， muscle cells， and liver cells， which resulting in insulin resistance. At the same time， the microRNA also played an role in damage of vascular endothelial cells and myocardial cell in diabetes. Conclusion MicroRNA acts an important role in the process of diabetes and its complications.
ObjectiveTo investigate the expressions of glucose transporter-4 (GLUT-4) and secreted protein acidic and rich in cysteine (SPARC) in adipose tissue of Goto-Kakizaki (GK)/Wister rats after gastric bypass operation (GBP), and to explore the possible mechanism of GBP improving insulin resistance.MethodsHealthy male GK rats were randomly divided into diabetic operation group (DO group, underwent GBP), diabetic sham operation group (DS group, underwent sham-operation), and diabetic control group (DC group, received no-treatment), Wister rats were set as normal control group (NC group, received no-treatment). The weight, fasting blood glucose (FPG), fasting serum insulin (Fins), and HbA1c were measured before operation and at the 1st, 2nd, 4th, and 8th week after operation. Quantitative insulin sensitivity check index (QUICKI) was measured in before operation and at the 8th week after operation, and the expressions of GLUT-4 and SPARC protein in adipose tissues were measured by Western Blot method at the 8th week after operative too.Results① Weight: the weight of the DO group was lower than preoperative at the 2nd and 4th week after GBP (P<0.05), but increased to the normal level at the 8th week after GBP (P>0.05). The weight of the DO group was lower than those of the DS group, DC group, and NC group at the same time point of 2nd, 4th, and 8th week (P<0.05). ② FPG: the FPG level of the DO group was lower than preoperative at the 2nd, 4th, and 8th week after GBP (P<0.05), and lower than those of the DS group and the DC group from 2nd to 8th week after GBP (P<0.05). The FPG level between the DS group and the DC group had no statistical significance (P>0.05). ③ Fins: the Fins level of the DO group was higher than preoperative at the 2nd week after GBP (P<0.05), and decreased gradually at 4th and 8th week but not significantly differed from the NC group at the same time point. At the 2nd week after GBP, the Fins level of the DO group was higher than those of the DS group and the DC group (P<0.05), but there was no statistical significance between the DS group and the DC group (P>0.05). ④ HbA1c: the HbA1c level of the DO group started to decrease but there was no statistical significance between preoperative and all time after GBP (P>0.05). There was no statistical significance among the 4 groups at the 8th week after GBP (P>0.05). ⑤ QUICKI: at the 8th week, the QUICKI value of the DO group was higher than preoperative (P<0.05), and at the same time, the QUICKI value of the DO group and the NC group were higher than those of the DS group and the DC group (P<0.05), but there was no statistical significance between the DO group and the NC group (P>0.05), as well as the DS group and the DC group (P>0.05). ⑥ GLUT-4 protein and SPARC protein: the expression of GLUT-4 protein of the DO group was dramatically higher than those of the DC, DS, and NC group (P<0.05), and the expression of SPARC protein of the DO group was dramatically lower than those of the DC, DS, and NC group (P<0.05) at the 8th week. But the expressions of GLUT-4 and SPARC protein had no statistical significance among the DS, DC, and NC group at the 8th week after GBP (P>0.05).ConclusionGBP may improve and increase the sensitivity of insulin resistance by regulating the expressions of GLUT-4 and SPARC protein in adipose tissue of GK rats.
Objective To evaluate the efficacy and safety of testosterone supplementary treatment for the middle-aged and the senile with insulin resistance (IR). Methods Such databases as PubMed (Jan. 1966 to July 2010), EMbase (Jan. 1984 to July 2010), The Cochrane Library (Issue 3, 2010), CBM (1978 to July 2010), CNKI (Jan. 1994 to July 2010), WanFang Data (1994 to July 2010) and VIP Data (1989 to July 2010) were searched. Randomized controlled trials (RCTs) about testosterone treatment for IR were included. Two reviewers independently extracted the data and evaluated the quality of the included studies. Meta-analyses were performed for the results of homogeneous studies by using RevMan 5.0 software, and other results not suitable for meta-analysis were described with qualitative analyses. Results Nine RCTs involving 573 patients were included. Of them, 308 cases were in the testosterone group and 265 in the placebo group. The baseline data of studies was comparable. The results of meta-analyses showed that, a) Efficacy: testosterone was superior to placebo in decreasing insulin resistance index (HOMA-IR) (WMD= –?0.56, 95%CI –?0.75 to –?0.37) and fasting insulin (FINS) (WMD= –2.4, 95%CI –3.25 to –1.56); and b) Safety: no significant difference was found in prostate specific antigen (PSA) (WMD= –?0.02, 95%CI –?0.22 to 0.18). Conclusion The testosterone supplementary treatment for insulin resistance is superior to the placebo, and there is no significant difference in PSA compared to the placebo. More multicenter double-blind RCTs in large-scale are required to verify this conclusion because of lack of high quality literature with large sample size.
ObjectiveTo explore the effect of gastric bypass (GBP) on metabolic syndrome (MS) and the related mechanisms. MethodsThe literatures addressed the effect of GBP on glucose metabolism and blood pressure were retrospectively analyzed. ResultsIt showed that GBP achieved durable level of blood glucose, remission of dylipidemia and hypertension, however, which occurred before significant weight loss. The changes of many factors such as food intake, gastrointestinal hormones, adipocytokines, fat distribution might be involved in GBP to improve MS. ConclusionGBP seems to achieve the control of MS as a primary and independent effect, rather than secondary to the treatment of overweight.
ObjectiveTo study effect of expression levels of serum inflammatory factors and insulin receptor substrate(IRS)-1/2 in visceral adipose tissue after Roux-en-Y gastric bypass(RYGB) on type 2 diabetes mellitus(T2DM) rats, and explore possible mechanism in treatment of T2DM. MethodsThe T2DM rats models were established, which were divided into 3 groups by intervention: T2MD-RYGB group(n=14), T2MD-sham operation(T2MD-SO) group(n=10), and T2MD group(n=10), and 10 normal rats were selected as control group. The rats of the T2MD-RYGB group were received the RYGB, and of the T2MD-SO group were received transection and reanastomosis of the gastroin-testinal tract. The fasting plasma glucose(FPG), fasting insulin(FINS), C-reaction protein(CRP), tumor necrosis factor-α(TNF-α), free fatty acid(FFA), homestasis model assessment for insulin resistance(HOMA-IR), adipose tissue insulin resistance(Adipo-IR) were tested respectively before operation and on week 1, 4, 8 after operation(synchronous detec-tion of rats with or without surgical intervention). The IRS-1 and IRS-2 protein contents of the rat epididymal adipose tissue were tested on week 8 after operation. ResultsThe FPG, FINS, CRP, TNF-α, FFA levels, and HOMA-IR, Adipo-IR indexes in the T2DM rats were significantly higher than those in the normal rats(P < 0.05) before operation, the above indicators on week 4, 8 after operation were significantly lower than those before operation in the T2MD-RYGB group(P < 0.05). The differences of changes among the other groups were not statistically significant(P > 0.05). The IRS-1 and IRS-2 protein expressions in the adipose tissue of the rats were significantly increased in the T2MD-RYGB group as compared with these indicators in the T2MD group and T2MD-SO group(P < 0.05), but which were significantly lower than those in the control group(P < 0.05). ConclusionsRYGB could increase IRS-1/2 expression levels in adipose tissue, which could enhance insulin sensitivity, decrease serum inflammatory factors levels, and improve insulin resistance ultimately. This might be one of the mechanisms in treatment of T2DM.
ObjectiveTo explore the clinical curative effect of high flux hemodialysis on diabetic nephropathy (DN) and impact on patients' insulin resistance (IR). MethodsA total of 96 patients with DN meeting the inclusion criteria treated between January 2013 and January 2014 were selected. The patients were randomly divided in to the observation group and control group with 48 in each. The control group received low flux hemodialysis, while the observation group underwent high flux hemodialysis. Before the treatment and in the first half of the year after the treatment, the clinical renal function and inflammatory indexes, lipid metabolism, and glucose metabolism related markers were recorded, and IR index (HOMA-IR) were calculated and compared. ResultsBefore and after the treatment, the Kt/V showed no significant change in the two groups (P > 0.05). Serum creatinine levels was lower after the treatment compared with that before the treatment in both of the two groups; in the observation group, C-reactive protein, interleukin-6 and tumor necrosis factorαwere significantly lower than those before the treatment and than those in the control group after the treatment (P < 0.05). HOMA-IR and fasting insulin levels in the observation group after the treatment were significantly lower than those before the treatment and than those in the control group after the treatment (P < 0.05). No significant changes of fasting plasma glucose and glycosylated hemoglobin levels in the two groups before and after the treatment in patients were found (P > 0.05). ConclusionHigh flux hemodialysis therapy is effective on DN, which can effectively remove the body and large molecular type of inflammatory mediators, alleviate the micro inflammatory state, improve the IR status and correct the lipid metabolic abnormalities.
ObjectiveTo summarize the research progress of correlation between pancreatic cancer and diabetes mellitus.MethodsRecent studies on the association between pancreatic cancer and diabetes mellitus were extensively reviewed, and relevant research results on the association between pancreatic cancer and diabetes mellitus were reviewed.ResultsPancreatic cancer had a particular association with diabetes. Patients with pancreatic cancer may develop new diabetes or worsen existing diabetes mellitus. About 50% of patients with pancreatic cancer had diabetes mellitus before diagnosis, suggesting a “dual causal relationship” between pancreatic cancer and diabetes mellitus. Long-term type 2 diabetes mellitus (T2DM) was one of the high risk factors for the occurrence and development of pancreatic cancer. T2DM may also increase the risk of pancreatic cancer due to hyperinsulinemia, adipokine, and other factors. Pancreatic cancer was one of the cause of diabetes mellitus at the same time, but its mechanism was not yet known, also needed to get a lot of information to understand the impact of long-term diabetes mellitus on the development of pancreatic cancer, as well as the reason of pancreatic cancer related to diabetes mellitus mechanism.ConclusionThe clear relationship between pancreatic cancer and diabetes mellitus has not been proved, and further research is needed to clarify the relationship between them.
ObjectiveTo systematically evaluate the changes in placental protein expressions in gestational diabetes mellitus (GDM) and their correlations with maternal insulin resistance (IR). Methods PubMed, Cochrane Library, Scopus, Web of Science, Embase, China National Knowledge Infrastructure, VIP database, Wanfang Database and CBMdisc were searched for case-control studies published from January 2009 to November 2021, which reported the placental protein expressions in GDM and their correlations with IR. Two researchers independently reviewed the literature, extracted data and evaluated the literature quality. RevMan 5.4 software was used for meta-analysis, and descriptive analysis was performed on data that cannot be combined. ResultsA total of 19 studies were included, comprising 2 012 patients. The results of meta-analysis showed that: the expression level of retinol binding protein 4 (RBP4) [standard mean difference=2.11, 95% confidence interval (CI) (1.64, 2.58), P<0.000 01] and the positive rate of protein tyrosine phosphatase-1B (PTP1B) [relative risk (RR)=1.56, 95%CI (1.29, 1.88), P<0.000 01] were up-regulated, and the positive rate of insulin receptor substrate 1 (IRS-1) [RR=0.69, 95%CI (0.60, 0.78), P<0.000 01] was down-regulated. The protein expression levels of RBP4 (P<0.000 01) and PTP1B (P<0.000 01) were positively correlated with homeostasis model assessment of insulin resistance (HOMA-IR), while the protein expression levels of IRS-1 (P<0.000 01) and APN (P=0.002) were negatively correlated with HOMA-IR, and glucose transporter 4 (GLUT 4) was not correlated with HOMA-IR (P=0.79). Descriptive analysis found that the expression levels or positive rates of adipocytokines (leptin, resistin), oxidative stress markers (xanthione oxidase, malondialdehyde, 8-isoprostaglandin),inflammatory factors (tumor necrosis factor α, Toll-like receptor 4, Galectin-3, Galectin-2, migration inhibitory factor),fetuin-A, forkhead box transcription factor 1, forkhead box transcription factor 3a and estrogen receptor α in GDM placenta were up-regulated and all were positively correlated with HOMA-IR. The expression levels or positive rates of insulin signaling pathway proteins [phosphoinositide 3-kinase (PI3K), protein kinases B (AKT), phospho-protein kinases B (p-AKT), GLUT 4] were down-regulated, PI3K and AKT were negatively correlatedwith HOMA-IR, while p-Akt had no correlation with HOMA-IR. ConclusionsThe dysregulation of placental protein expressions may mediate maternal IR exacerbation, thus promote the occurrence and development of GDM and other pregnancy complications. The causal relationship and regulatory mechanism are still unclear, which need to be further studied.