Efficacy of antihyperglycemic drugs and inositol on polycystic ovary syndrome: A network meta-analysis / 中华内分泌代谢杂志

Objective:The study was designed to evaluate the efficacy in polycystic ovary syndrome (PCOS) of glucagon-like peptide-1 receptor agonists (GLP-1RA), metformin combined with thiazolidinediones, α-glucosidase inhibitor, and inositol.Methods:Eligible studies were searched in databases of PubMed, EMBase, Cochrane Library, Wanfang data, and CNKI based on population, interventions, comparisons, outcomes, and study design (PICOS) principle (inception to Nov 2020). Two researchers independently screened randomized controlled trials in strict accordance with the inclusion and exclusion criteria, extracted basic information and outcomes of included studies, and used Cochrane risk of bias tool to evaluate the methodological quality of the literature. Network meta-analysis was conducted by STATA 14.0. Continuous variables without dimensional differences were calculated by weighted mean difference and 95% CI, and continuous variables with dimensional differences were calculated using standardized mean difference and 95% CI. Results:A total of 27 studies with 1 445 patients were included in this study. Network meta-analysis showed that acarbose presented a better efficacy than other interventions in reducing total testosterone [surface under the cumulative ranking curve (SUCRA): 89.4%]. GLP-1RAs may have the best efficacy in reducing body mass index and homeostasis model assessment for insulin resistance (HOMA-IR; SUCRA: 99.1%, 89.2%, respectively), while using inositol may be a good choice to reduce serum fasting insulin, HOMA-IR, blood total cholesterol, and blood triglycerides (SUCRA: 94.5%, 85.4%, 96.6%, and 82.8%, respectively).Conclusions:Acarbose may have advantages over other antihyperglycemic drugs in lowering blood testosterone. GLP-1RAs are more helpful to improve body mass index and HOMA-IR in PCOS patients. Inositol, as an insulin sensitizer, has a favorable effect on reducing fasting insulin, HOMA-IR, blood total cholesterol, and blood triglycerides, and there are no reports of side effects in current researches. Further study is still needed to confirm its efficacy.

Progress in diagnosis and therapy of polycystic ovary syndrome / 中华内分泌代谢杂志

The etiology of polycystic ovary syndrome(PCOS) is unknown, which is closely related to insulin resistance and hyperinsulinemia. There are several controversies on PCOS diagnosis because of its diversity and heterogeneity in clinical manifestations. PCOS biomarkers have become a research hotspot. The methods of treatment include lifestyle interventions and improving metabolic dysfunction, hyperandrogenism, and reproduction abnormality. This article reviews the latest research progress in the morbidity characteristics, diagnostic criteria, and the therapy of PCOS.

Progress in diagnosis and therapy of polycystic ovary syndrome / 中华内分泌代谢杂志

The etiology of polycystic ovary syndrome(PCOS) is unknown, which is closely related to insulin resistance and hyperinsulinemia. There are several controversies on PCOS diagnosis because of its diversity and heterogeneity in clinical manifestations. PCOS biomarkers have become a research hotspot. The methods of treatment include lifestyle interventions and improving metabolic dysfunction, hyperandrogenism, and reproduction abnormality. This article reviews the latest research progress in the morbidity characteristics, diagnostic criteria, and the therapy of PCOS.

Comparative study of efficacy and safety of compound pioglitazone hydrochloride glimepiride tablet and glimepiride tablet in treating type 2 diabetes mellitus / 重庆医学

Objective To compare the efficacy and safety of compound pioglitazone hydrochloririe glimepiride tablet and glimepiride tablet in the treatment of type 2 diabetic mellitus(T2DM) for evaluating the effectiveness and safety of compound pioglitazone hydrochloride glimepiride tablet for treating T2DM.Methods The random,double-blind,double-dummy,positive drugs parallel control clinical study method was adopted.Thirty-three T2DM patients with poorly controlled blood glucose were randomly assigned to the test group(n=22) and control group(n=11) by the 2 ∶ 1 ratio.The test group was given compound pioglitazone hydrochloride glimepiride tablet,while the control group received glimepiride tablet.The treatment cycle was 12 weeks.The differences of FBG,HbA1c,FINS and HOMA-IR in the two groups were compared between before and after treatment.Moreover the changes of body mass,blood pressure and blood lipids as well as adverse events occurrence were compared between the two groups.Results Thirty-one cases finished the treatment follow up(21 cases in the test group and 10 cases in the control group);the decreased amplitudes of HbA1c levels after 12-week treatment in the test group and control group were (0.99 ± 1.87)％ and (-0.02 ± 0.90) ％ respectively,which of FPG were (0.94 ± 1.87) mmol/L and (0.37 ± 2.62) mmol/L respectively.The FPG and HbA1c levels after treatment in the test group were decreased compared with before treatment,the difference was statistically significant (P＜0.01).The change difference of FPG and HbA1c in the control group had no statistical difference(P＞0.05).FINS and HOMO-IR in the test group were significantly decreased before and after treatment,the difference was statistically significant (P＜0.01).The incidence rate of hypoglycemia had no statistically significant difference between the test group and control group.Conclusion The effectiveness of compound pioglitazone hydrochloride glimepiride tablet in treating T2 DM is superior to the single use of glimepiride,while the safety is equivalent to single use of glimepiride.

Effects of JAZF1 overexpression on proinflammatory cytokines in hepatocytes induced by palmitic acid / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of JAZF1 overexpression on the pro-inflammatory cytokines in hepatic steatosis.</p><p><b>METHODS</b>The model of hepatic steatosis was established by incubating hepatocytes with palmitic acid (PA) at 0, 0.125, 0.25, 0.5 and 1 mM dose and for 0, 6, 12, 24 and 48 hours, after which recombinant adenovirus expressing JAZF1 (Ad-JAZF1) was introduced to up-regulate expression. Triglyceride level was measured by GOD. Cell viability was detected by CCK-8. The mRNA and protein expression of TNF-alpha, MCP-1, IL-8 and JAZF1 was examined by RT-PCR, ELISA, and western blotting.</p><p><b>RESULTS</b>The PA-treated hepatocytes showed dose-dependent significant increases in TNF-alpha, MCP-1 and IL-8 mRNA expression for doses up to 0.25 mM; there were no significant increases for the highest doses of 0.5 and 1 mM. The 0.25 mM PA-treated hepatocytes showed time-dependent significant increases in TNF-alpha, MCP-1 and IL-8 mRNA expressions (FTNF-alpha = 26.51, FMCP-1 = 57.20, FIL-8 = 353.85, P less than 0.01), with the maximum level reached at 12 h and followed by a gradual decrease with longer treatment times. JAZF1 mRNA and protein expression was markedly increased in hepatocytes infected with Ad-JAZF1 (P less than 0.01). However, the AP-treated hepatocytes with JAZF1 overexpression showed down-regulation of TNF-alpha, MCP-1 and IL-8 mRNA expression (decreased by 89.69%, 77.68%, and 83.21%, respectively) and secretion (37%, 37% and 41%, respectively, P less than 0.01).</p><p><b>CONCLUSION</b>Stimulation of hepatocytes by the PA fatty acid in vitro promotes mRNA expression of TNF-alpha, MCP-1 and IL-8, but overexpression of JAZF1 inhibits the PA-induced expression and secretion of these factors.</p>

Changes of urine adiponectin levels and relevant factors in the population with different stage of diabetic nephropathy / 重庆医学

Objective To investigate urine adiponectin changes and related factors in different stage of type-2 diabetic ne-phropathy.Methods A total of 1 1 9 DN patients admitted to the Yongchuan Hospital of Chongqing Medical University in 2013 were selected.The general indices and laboratory examination results were retrospectively analyzed.1 1 9 type-2 diabetic nephropathy patients were divided into normal Proteinuria group,micro-Proteinuria group,macro-Proteinuria group,according to urine albumin excretion rate in 24 hours.45 health subjects from Physical examination center were enrolled as normal group.The UAER of the three groups were compared and the correlation between each index and UAER was analyzed.Results Urine adiponectin levels in normal Proteinuria group was significantly lower than micro-Proteinuria group(P <0.01)and macro-Proteinuria group(P <0.01). Urine adiponectin levels in micro-Proteinuria group was significantly lower than macro-Proteinuria group (P <0.01)and higher than normal group(P < 0.01 ).Urine adiponectin levels in macro-Proteinuria group were significantly higher than normal group (P <0.01 ).Multiple linear regression analysis showed that HDL-C,FPG,HbA1c and UAER had effects on the levels of Urine adiponec-tin.Conclusion Urinary adiponectin levels are associated with type 2 diabetic nephropathy,and which was related with HDL-C, FPG,HbA1c and UAER.

Efficacy of parathyroid hormone (1-34) and elcatonin in postmenopausal women with osteoporosis：A randomized and controlled trial for 18 months / 中华内分泌代谢杂志

Objective Recombinant human parathyroid hormone(1-34) [ rhPTH(1-34)] is the unique anabolic substance acting on the skeleton. The efficacy and safety of long-term administration of rhPTH(1-34) in Chinese postmenopausal women have not been evaluated. This study compared the clinical efficacy and safety of rhPTH(1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. Methods A total of453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH(1-34) 20 μg(200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine ( L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover ( serum bone-specific alkaline phosphatase was measured by radioimmunoassay; C-telopeptide/ creatinine ( CTX/ Cr) measured by quantitative sandwich enzyme-linked immunosorbent assay) at 6, 12, and 18 months. Adverse events were recorded. Results rhPTH(1-34) increased lumbar BMD more significantly than that did by elcatonin at 6 months( M6), 12 months (M12), and 18 months(M18; 4. 3% vs 1. 94% , 6. 8% vs 2. 72% , 9. 51% vs 2. 86% , P<0. 01). There was only a small but significant increase of femoral neck BMD at M18(2. 64% , P<0. 01) in rhPTH(1-34) groups. There were greater increases in bone turnover markers in the rhPTH(1-34) group than in the elcatonin group at M6, M12, and M18[serum bone-specific alkaline phosphatase(BSAP) 93. 67% vs -3. 56% , 117. 78% vs -4. 12% , 49. 24% vs-5. 81% , P<0. 01; urinary CTX/ Cr 250% vs -29. 5% , 330% vs -41. 4% , 273 % vs -10. 6% , P<0. 01]. rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5. 36% (6 / 112) in elcatonin group and 3. 23% ( 11 / 341 ) in rhPTH ( 1-34 ) group ( P = 0. 303 ). Both treatments were well tolerated. Hypercaluria(9. 38% ) and hypercalcemia(7. 04% ) in rhPTH(1-34) group was transient and caused no clinical symptoms. Pruritus(8. 21% vs 2. 68, P=0. 044) and redness of injection site(4. 40% vs 0, P=0. 024) were more frequent in rhPTH(1-34). Nausea / vomiting(16. 07% vs 6. 16% , P = 0. 001) and hot flushes(7. 14% vs 0. 59% , P<0. 001) were more common in elcatonin group. Conclusion rhPTH(1-34) treatment was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months treatment. rhPTH(1-34) could ameliorate back pain effectively. The results of the present study indicate that rhPTH(1-34) is an effective, and safe agent in treating postmenopausal women with osteoporosis.

Zinc-finger BED domain-containing 3 expression in tissues of various organs in normal C57BL/6J mice and the changes in the ZBED3 expression levels affected by liraglutide in C57BL/6J mice and db/db mice / 中华内分泌代谢杂志

Objective To compare zinc-finger BED domain-containing 3 ( ZBED3 ) expression in various tissues of C57BL/6J mice and the effects of liraglutide, glucose, and insulin on the levels of ZBED3 protein expression in C57BL/6J mice and db/db mice. Methods The mRNA level of ZBED3 in various tissues of C57BL/6J mice was measured by realtime PCR. The protein level of ZBED3 was measured by using western blot. Results ZBED3 mRNA levels were detected in muscle, spleen, kidney, brain, heart, lung, and liver of C57BL/6J mice, yielding the highest expression in muscle. Additionally, The liver ZBED3 levels were higher in db/db mice compared with C57BL/6J mice (P<0. 01). Furthermore, the protein expression of ZBED3 was significantly increased in liver tissues of db/db mice treated with high concentrations of liraglutide, glucose or insulin(P<0. 05), however, the expression of ZBED3 only responded to high concentration of glucose in liver tissues of C57BL/6J mice. Conclusion ZBED3 may act as a novel factor in regulating glucose metabolism. The expression of ZBED3 can be regulated by liraglutide, glucose, and insulin. Thus, ZBED3 may play an important role in conditioning of hyperglycemia.

Expression of secreted frizzled related protein 5 in human adipose and muscle tissues and their relation with insulin resistance / 中华内分泌外科杂志

Objective To investigate the change expression levels of secreted frizzled related protein 5 (SFRP5) mRNA and protein in human adipose,and muscle tissues and the relationship between SFRP5 and insulin resistance in different glucose tolerance subjects.Methods Twelve type 2 diabetes mellitus(T2DM) patients and 12 aged and sex-matched healthy control subjects were enrolled.T2DM patients were diagnosed by1999 WHO criterion.Under the same conditions,the omental adipose and muscle tissues from these patients undergoing elective abdominal surgery were obtained.Expressions of sfrp5 protein and mRNA in adipose and muscle tissues were determined by semi—quantitive RT-PCR and Western blot while body height,weight,waist circumference,hipcircumference,blood pressure,lipodemia,fasting plasma glucose,fasting insulin,glycosylated hemoglobin,fasting serum insulin(FINS),HOMA-β,HOMA-insulin resistance index(HOMA-IR) etc were investigated.Results 1.SBP,TG,FPG,2 h PG,Fins,HOMA-IR,HbA1C were significantly higher in T2DM groups than in the control group.2.The expressions of SFRP5 mRNA and protein in omental adipose tissues were significantly higher inT2DM group than in the control group(P ＜ 0.01).3.The level of SFRP5 mRNA and protein expressions were higher in omental adipose tissue than in the muscle tissues.Conclusions The fact that mRNA and protein expression level of SFRP5 was higher in adipose tissue than in muscle indicates adipose tissue may be the main source of SFRP5.The expressions of SFRP5 mRNA and protein were higher inT2DM group than in the control group indicates sfrp5 may play a role in insulin resistance.

The correlation between zinc-α2-glycoprotein and adiponectin in population with different glucose tolerance / 中华内分泌代谢杂志

Objective To investigate the relationship of circulating zinc-α2-glycoprotein (ZAG) as well as adiponectin with adiposity and insulin resistance in humans.Methods Serum ZAG and adiponectin levels were determined by ELISA in 285 subjects with normal glucose tolerance (NGT),impaired glucose tolerance (IGT),and newly diagnosed cases with type 2 diabetes mellitus(T2DM).The relationships between circulating ZAG and insulin resistance or metabolic parameters were also explored.Results Circulating ZAG and adiponectin levels were all lower in T2 DM and IGT subjects than those in control subjects [ZAG:(37.14 ± 13.25 and 48.84 ± 18.74 vs 59.36 ± 16.20) mg/L,P＜0.05 or P＜0.01 ; adiponectin:(27.79 ± 11.23 and 33.00 ± 9.42 vs 41.81 ± 13.68) μg/L,P＜0.01].Circulating ZAG was correlated positively with high density lipoprotein-cholesterol and adiponectin (all P＜0.01),and inversely with body mass index,waist-hip ratio,FAT％,diastolic blood pressure,triglyceride,fasting blood glucose,fasting insulin,HbA1C,and homeostasis model assessment for insulin resistance(HOMA-IR,P＜0.05 or P＜0.01).By multivariate analysis,ZAG levels were independently associated with body mass index,HOMA-IR,diastolic blood pressure,and adiponectin (P＜0.05 or P＜0.01).Conclusions ZAG levels,associated with fat,insulin sensitivity,and adiponectin expression,are likely to play an important role in insulin resistance and energy homeostasis in humans.

Effect of mitiglinide calcium on fasting plasma fibroblast growth factor-21 level in patients with newly diagnosed type 2 diabetes mellitus / 中华内分泌代谢杂志

Eighty-two newly-diagnosed type 2 diabetic patients with poor glycemic control were treated by mitiglinide calcium for 16 weeks.Plasma fibroblast growth factor-21 ( FGF-21 ) level were evaluated.The relationship of plasma FGF-21 levels with body mass index,body fat,waist-to-hip ratio,lipid,blood glucose,HbA1c,and free fatty-acid were analyzed.Plasma FGF-21 was decreased significantly by treatment with mitiglinide calcium in type 2 diabetic patients,and it may play a role in the pathogenesis of type 2 diabetes mellitus.

Effects of recombinant human parathyroid hormone (1-34) and elcatonin on bone metabolism and serum SPARC in postmenopausal women with osteoporosis / 中华内分泌代谢杂志

ObjectiveTo investigate the effect of rhPTH (1-34) and elcatonin on bone metabolism and serum secreted protein acidic and rich in cysteine ( SPARC ) in postmenopausal women with osteoporosis.Methods One hundred and twenty-four postmenopausal women with osteoporosis were randomly divided into 2 groups:One group was treated with recombinant human parathyroid hormone ( 1-34 ) [ rhPTH ( 1-34 ) ] 200 U/d by subcutaneous injection (PTH group,n =89 )and another group was treated with elcatonin 20 U/week by intramuscular injection (CT group,n =35 ) for 12 months.All patients received a basic therapy with oral calcium ( Ca 600 mg+ Vit D3125 U,q..d.).The bone mineral density ( BMD ) of lumbar spine( L2-4 ),the left femoral neck,greater trochanter,and Ward's triangle,serum calcium and phosphate were measured by baseline,6 months' and 12 months.Levels of serum bone-specific alkaline phosphatase( BSAP),serum secreted protein acidic and rich in cysteine (SPARC)were determined by an ELISA assay.ResultsBy 12 months,rhPTH ( 1-34 ) treatment significantly increased the lumbar spine L2-4 BMD 7.9％ (P＜0.05),serum calcium 8.3 ％ ( P＜ 0.05 ),serum BSAP 93.4％ ( P＜ 0.05 ),serum SPARC by 12.6％[ ( 195.68±59.57 vs 173.81 ±81.33 ) pμg/L,P＜0.05 ].Elcatonin therapy increased the lumbar spine L2-4 BMD by 3.2％ (P＜0.05) at the end of 12 months,but elcatonin did not influence serum calcium,BSAP and SPARC.The rhPTH( 1-34 ) increased lumbar spine L2-4 BMD more than elcatonin did at 12 months( P＜0.05 ).ConclusionrhPTH (1-34) could promote the bone anabolism more effectively than elcatonin did.Serum SPARC may play an important role in promoting osteogenesis by rhPTH.

Changes of plasma nesfatin-1 levels in patients with impaired glucose regulation and type 2 diabetes mellitus / 中华内分泌代谢杂志

Plasma nesfatin-1 levels were assayed by ELISA in patients with impaired glucose regulation (IGR),type 2 diabetes mellitus( T2DM ),and healthy subjects with normal glucose tolerance( control group).The results showed that plasma nesfatin-1 levels in IGR and T2DM groups were significantly higher than that in control group [ ( 1.91 ±0.79 and 1.80±0.80 vs 1.41 ±0.58) μg/L,P＜0.01 ].Plasma nesfatin-1 levels were positively correlated with body mass index(BMI),HbA1c,waist hip ratio,fasting plasma glucose,fasting insulin,and homoestasis model assessment insulin resistant index( HOMA-IR,P＜0.05 or P＜0.01 ).Multiple regression analysis showed that BMI and HOMA-IR were independent related factors in influencing plasma nesfatin-1 levels (both P＜0.01 ).These results suggest that nesfatin-1 may partially contribute to the pathogenesis of insulin resistance and T2DM.

Effects of liraglutide on fibroblast growth factor-21 and its receptors in insulin-resistant mice with hypoadiponectinemia / 中华内分泌代谢杂志

The effects of liraglutide on glucose and lipid metabolism, fibroblast growth factor-21 ( FGF-21 )and its receptors (FGFR) in APoE-/-mice with hypoadiponectinemia were investigated.Hypoadiponectinemia facilitated disturbance in glucose and lipid metabolism and insulin resistance. Compared with the control mice, FGF21 mRNA and protein expressions of liver and adipose tissues as well as plasma FGF-21 level were significantly increased in ApoE-/-mice with hypoadiponectinemia, along with lowered expressions of FGFR1 and β-klotho mRNA in adipose tissues, and expressions of FGFR1-3 and β-klotho mRNA in liver. Liraglutide administration improved glucose and lipid metabolism and insulin resistance, and partially reversed the changes of FGF-21 and its receptors induced by hypoadiponectinemia.

Effects of FGF-21 gene knockdown on glucose and lipid metabolism in ApoE-/- mice / 中华内分泌代谢杂志

ObjectiveTo investigate the in vivo effects of down-regulating the FGF-21 gene expression by shRNA on glucose and lipids metabolism in high fat diet (HFD) fed ApoE-/- mice.MethoedsMale ApoE-/- mice were randomly divided into chow diet (CF)fed group ( NF,n =10),CF fed + pAd-shFGF-21 group ( NFG,n =9),and HFD fed group ( HF,n =10),HFD fed + Adv-null vector ( pAd-GFP ) group ( GFP,n =6) and HFD fed + pAd-shFGF-21 group ( HFG,n =10).Mice were fed for 16 weeks.C57BL/6J mice were set as control group ( NC group,n=10).NFG,HFG,and GFP groups were injected with pAd-shFGF-21or pAd-GFP by tail vein at the end of 15 weeks.The insulin sensitivity and glucoselipid metabolism were assessed by the hyperinsulinemic- euglycemic clamp technique using 3-[ 3 H] glucose as a tracer at the end of 16 week.ResultsThe plasma FGF-21 levels in NFG and HFG groups were significantly degraded than those in NF and HF groups(20％-27％,P＜0.05),respectively.In the basal state,the fasting blood glucose,fasting plasma insulin,free fatty-acids,triglycerides,total cholesterol,and LDL-C were significantly higher,while the HDL-C was lower in NFG and HFG groups compared with those in NF and HF groups,respectively (P＜0.05 or P＜0.01 ).During the steady-state of clamp,FFA was suppressed in all groups,but it was still higher in NFG and HFG groups than NF and HF groups ( P＜0.05or P＜0.01 ).The glucose infusion rate (GIR)and glucose disappearance rate (GRd)in NFG and HFG groups were significantly decreased compared with NF and HF groups (all P＜0.01 ).In addition,insulin's ability to suppress hepatic glucose production (HGP) during clamps was significantly decreased in HFG and NFG group compared with HF and NF groups (49％ and 20％,respectively; all P＜0.01 ).ConclusionFGF-21 knockdown and low FGF-21 level facilitate the development of metabolic disorder and insulin resistance.

Effects of tumor suppressor in lung cancer-1 overexpression on gene expressions involved in glucose and lipid metabolism in liver cells / 中华内分泌代谢杂志

The effects of tumor suppressor in lung cancer-1(TSLC1)upregulation on gene expressions involved in glucose and lipid metabolism in Hepa1-6 cells were investigated.The results showed that TSLC1 overexpression decreased fatty acid synthase and acetyl CoA carboxylase expressions(P<0.05 or P<0.01),increased adipose triglyceride lipase expression(P<0.05),and did not change hormone-sensitive lipase,glucose transporter (GLUT)1,and GLUT4 expressions.These results suggest that TSLC1 overexpression may promote lipolysis and inhibit adipogenesis in liver cells.

Effects of liraglutide on the expression of genes related to cholesterol metabolism in ApoE-/-mice with hypoadiponectinemia / 中华内分泌代谢杂志

Objective To investigate the effects of liraglutide on gene expression related to cholesterol metabolism in ApoE-/-mice with adiponectin deficiency. Methods Thirty six ApoE-/-mice fed with the high-fat diet were subdivided into four groups. One group was given 100 μl(1×109PFU) of adenoviral pAd-U6-GFP(GFP group, n=6). The second group received 100 μl of adenoviral pAd-U6-Acrp30(ADI group, n=10). The third group was given 100 μl of adenoviral pAd-U6-Acrp30 and liraglutide(HEA group, n=10) and the fourth group was given only 100 μl sterile saline(HF group, n=10). Insulin sensitivity and glucose metabolism were assessed by the hyperinsulinemic-euglycemic clamp technique using 3-[3H] glucose as a tracer. Plasma adiponectin level was evaluated using a commercially available ELISA kit. The mRNA expressions of genes involved in cholesterol metabolism were measured by quantitative realtime PCR. Results Fasting blood glucose(FBG), free fatty acids(FFA), total cholesterol, triglyceride, low density lipoprotein cholesterol, adiponectin, and fasting plasma insulin(FINS) in ADI mice were significantly higher than those in the other groups(P＜0.01), while high density lipoprotein cholesterol was significantly lower(P＜0.05). During the clamp, glucose infusion rate(GIR) in ADI group was significantly lower than the other groups(P＜0.01), and hepatic glucose production(HGP) significantly higher in ADI group(P＜0.01). The mRNA expressions of INSIG2 and LDLR in ADI group were significantly down-regulated in HEA group(P＜0.01 or P＜0.05), while HMGCR and SREBP-2 were significantly up-regulated in HEA group(P＜0.01 or P＜0.05). Conclusions Liraglutide regulates a number of genes involved in cholesterol metabolism and ameliorates hypercholesterolemia by elevating plasma adiponectin level.

Effects of Liraglutide on plasma fibroblast growth factor-21 level in patients with type 2 diabetes mellitus / 中华内分泌外科杂志

Objective To investigate the effects of Liraglutide on plasma FGF-21 level in patients with type 2 diabetes mellitus (T2DM). Methods Enzyme linked immunosorbent assay (ELISA) was used to measure plasma FGF-21 level in patients with T2DM and normal controls (NGT). Relationship between plasma FGF-21level and BMI, WHR, HOMA-IR, HOMA-IS, FFA was analyzed. After Liraglutide treatment, plasma FGF-21level was observed in patients with T2DM. Results Fasting plasma FGF-21 level was higher in T2DM patients than that in normal control group ( 1.81 ±0.32 vs. 1.32 ±0.09 μg/L, P ＜0.01 ). After Liraglutide treatment, WHR, BMI, FPG, 2hPBG, HbA1c and FFA in T2DM patients significantly decreased ( P ＜0.05 or P ＜0. 01 ),HOMA-IS remarkably increased (P ＜ 0. 01 ), and FGF-21 had no change. Conclusion Liraglutide and FGF-21may have different roles in insulin resistance.

The efficacy and safety of recombinant human insulin injection in the treatment of diabetic patients: a multicenter, randomized, controlled and open-labled clinical trial / 中华内科杂志

Objective A multicenter, randomized, controlled and open-labled clinical trial was performed to compare the efficacy and safety of recombinant human insulin injection ( Yousilin R) and treated with Yousilin R versus Novolin R for 12 weeks respectively. Results Compared with baseline,the levels of glycosylated hemoglobin A1c ( HbA1c ) at the end of 12 weeks treatment decreased from 10. 77% to 7. 72% ( P ＜0. 05 ) in Yousilin R group and from 10. 33% to 7. 62% ( P ＜0. 05 ) in Novolin R group,2-hour postprandial plasma glucose ( 2hPG ) decreased from 15.49 mmol/L to 9. 72 mmol/L ( P ＜ 0. 05 ) in Yousilin R group and from 15.33 mmol/L to 10. 07 mmol/L( P ＜ 0. 05 ) in Novolin R group, and fasting plasma glucose (FPG) decreased from 10. 90 mmol/L to 7. 31 mmol/L( P ＜0. 05 ) in Yousilin R group and from 10. 22 mmol/L to 7.21 mmol/L (P ＜0. 05) in Novolin R group. The changes of HbA1c, 2hPG and FPG from baseline to endpoint in Yousilin R group was similar to those in Novolin R group ( P ＞ 0. 05 ).Furthermore, hypoglycemic events(26. 42% vs 30. 48% ), other adverse events( 13.21%vs 16. 19% ) ,and serious adverse events( 1.89%vs 1.90% )were comparable between Yousilin R and Novolin R groups(P ＞0. 05 ). Conclusions Yousilin R has similar efficacy, safety and compliance profiles to Novolin R group in the treatment of diabetic patients.

Effect of novel gene JAZF1 overexpression on glucose and lipid metabolism in 3T3-L1 adipocytes / 中华内分泌代谢杂志

Objective To observe the effects of JAZF1 (Juxtaposed with another zinc finger gene 1 ) overexpression on glucose and lipid metabolism in 3T3-L1 adipocytes. Methods The tissue distribution of JAZF1 in healthy C57BL/6J mice was detected by real-time quantitative PCR( RT-QPCR). Expression vector for JAZF1 gene was constructed and transfected into 3T3-L1 adipocytes. The mRNA levels of JAZF1, GLUT1, GLUT4, FAS, ACC, SREBP1, ATGL, and HSL implicated in glucose and lipid metabolism were determined by RT-QPCR; JAZF1 protein level was measured by Western blot. Intracelluar lipid accumulation were measured by oil red O staining method. Results In JAZF1-transfected adipocytes, JAZF1 mRNA and protein levels were significantly higher than control cells after 48 h. The mRNA level of HSL was increased significantly (P<0. 05) in JAZF1 transfection group compared with negative control and empty vector group, and the expressions of FAS, ACC, SREBP1 mRNA were decreased significantly(all P<0.01). However, the mRNA levels of ATGL, GLUT1, GLUT4 were not changed. Intracelluar lipid accumulation was decreased significantly (P<0.05 ) by oil red O staining and colorimetric in JAZF1 -transfected cells compared with negative control and empty vector group. Conclusions There was an extensive expression of JAZF1 in various tissues of C57BL/6J mice,indicating that JAZF1 might play a role in maintaining normal physiological function. These results show that overexpression of JAZF1 in 3T3-L1 cells can reduce lipid synthesis, increase lipolysis, and improve lipid accumulation. JAZF1 might provide a new potential therapeutic target for obesity and diabetes.