The effects of insulin and gliclazide therapy on endoplasmic reticulum stress and insulin sensitivity in liver of type 2 diabetic rats / 中华内科杂志

Objective To investigate the effect of insulin and gliclazide therapy on endoplasmic reticulum (ER) stress and insulin sensitivity in the liver of type 2 diabetic rats.Methods A high fat diet plus a low-dose of streptozotocin was implemented to create a type 2 diabetic rats which were randomly divided into diabetes mellitus (DM) group,insulin treatment (INS) group and gliclazide treatment (GT)group; and healthy rats were as normal control group.Diabetic rats in INS and GT groups were given neutral protamine hagedorn (NPH) insulin and gliclazide respectively for 3 weeks.Protein expression levels of immunoglobulin binding protein (Bip),spliced X-box binding protein 1 (XBP-ls),phosphorylated c-Jun on serine 73 (p-c-Jun),phosphorylated insulin receptor substrate 1 on serine 307 (p-IRS-1),and glucose-6-phosphatase (G6Pase) in liver homogenate were detected by Western blotting.Results Compared with the normal rats,Bip and XBP-Is in the DM group were up-regulated (0.28 ±0.07 vs 0.90 ±0.10 for Bip;0.41 ± 0.07 vs 0.95 ±0.07 for XBP-1 s; both P ＜ 0.01 ) ; p-c-Jun (0.59 ± 0.18 vs 1.94 ± 0.03 ),p-IRS-1( 1.73 ± 0.18 vs 5.32 ± 0.22) and G6Pase (0.11 ± 0.01 vs 0.45 ± 0.01 ) were increased ( all P values ＜0.01 ).In the INS group,all of aforementioned changes were reversed (0.90 ± 0.10 vs 0.25 ± 0.04 for Bip; 0.95 ±0.07 vs 0.47 ±0.01 for XBP-1s; 1.94 ± 0.03 vs 0.50 ±0.10 for p-c-Jun; 5.32 ± 0.22 vs 1.59 ±0.32 for p-IRS-1 ; 0.45 ±0.01 vs 0.15 ±0.02 for G6Pase,all P values ＜0.01 ).In the GT group,all of aforementioned changes were also attenuated ( 0.90 ± 0.10 vs 0.53 ± 00.02 for Bip ; 0.95 ± 0.07 vs 0.78±0.02 for XBP-1s; 1.94 ±0.03 vs 1.33 ±0.11 for p-c-Jun; 5.32 ±0.22 vs 3.13 ±0.02 for p-IRS-1; 0.45 ± 0.01 vs 0.25 ± 0.01 for G6Pase,all P values ＜ 0.05).Furthermore,all of aforementioned protein levels were down-regulated more obviously in the INS group comparing to the GT group ( all P values ＜ 0.01 ).Conclusions Both insulin and gliclazide therapy could relieve ER stress and e-Jun N-terminal kinase activity and improved insulin sensitivity.The effect of insulin on Bip,XBP-1s,p-c-Jun,p-IRS-1 and G6Pase protein expressions is more obvious than that of glilcazide,which indicates besides lowering glucose,insulin might have protective effects of anti-inflammation,anti-oxidative stress or stimulation of lipid redistribution.

Effect of early insulin therapy on nuclear factor-kB inflammatory pathway in liver of diabetic rat / 中华内科杂志

Objective To investigate the effect of early insulin therapy on NF-KB pathway and inflammatory cytokine responses in fiver of diabetic rat.Methods NF-KB p65 DNA binding was assayed with ELISA-based assay kit,cytokine gene expressions were quantified with real-time PCR and phosphoenolpyruvate carboxykinase(PEPCK),NF-KB and inhibitor KB(IKBα)protein levels wlere assayed with Westem blot.Results Compared with control,hepatic PEPCK protein level in the untreated diabetic rat increased by 40%.Early insulin and gliclazide treatment normalized PEPCK protein level.The abundance of IKBα protein was significantly decreased and nuclear NF-KB p65 DNA binding activity was incteased in untreated diabetic rats.IKBot protein content increased and NF-KB p65 DNA binding decreased during early intervention treatment.mRNAs encoding IL-1β and TNFα were increased,which were reduced to normal levels after insulin and gliclazide treatment.Conclusions It is suggested that early insulin treatment inhibits NF-KB activity and inflammatory cytokine responses in fiver that are involved in the aniefioration of insulin resistance in diabetic rats.Such results misht be due to indirect antiinflammatory effects of insulin thus relieving glucotoxicity and lipotoxicity in pefipherM tissues.

Identification of a novel glucokinase-E339K mutation in a Chinese maturity onset diabetes of the young 2 pedigree / 中华内科杂志

ovel GCK-E339K mutation might be linked to this MODY2 pedigree.

Screening for Mutations of MODY 1-5 Genes in Chinese Families with Early-onset Type 2 Diabetes / 中山大学学报(医学科学版)

[Objective] The aim of our study was to seek the mutations in MODY1～5 genes in Chinese population by direct sequencing in probands from families with early-onset type 2 diabetes.[Methods] Variants screening in MODY 1-5 genes were performed by PCR and direct sequencing in 19 probands from early-onset type 2 diabetes families.[Results] We found no mutation but many polymorphisms.There were 6,5,15,1,and 1 variants in MODY 1-5 genes respectively.[Conclusion] Our negative results in MODY genes suggest the genetic heterogeneity of different populations.Mutations in MODY 1-5 genes might not be the cause of diabetes in those 19 families.

Association of Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 gene with type 2 diabetes mellitus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 gene with type 2 diabetes mellitus and its clinical characteristics.</p><p><b>METHODS</b>The genotypes of Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 gene were determined by polymerase chain reaction-restriction fragment length polymorphisms assay in 401 unrelated subjects of the Han population in the southern part of China (including 180 subjects with normal glucose tolerance and 221 type 2 diabetic patients). The clinical data were also analyzed.</p><p><b>RESULTS</b>The allele frequencies in the case and control groups were 96.15%,96.11% for P and 3.85%, 3.89% for A; the genotype frequencies were 92.77%, 92.22% for PP, 6.78%, 7.78% for PA and 0.45%, 0 for AA. The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 was not significantly associated with type 2 diabetes. The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma2 in diabetes patients was associated with increased waist circumference and waist to hip ratio. The Pro12Ala polymorphism in Chinese population was similar to that in Japanese population and was different from that in European and American population.</p><p><b>CONCLUSION</b>The above data showed that the Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 was not significantly associated with type 2 diabetes, but it could be associated with abdominal obesity in type 2 diabetes. The significant difference of Pro12Ala of peroxisome proliferator-activated receptor-gamma2 among various races was observed.</p>

Molecular defects in persistent hyperinsulinemic hypoglycemia in infants / 中华内分泌代谢杂志

Persistent hyperinsulinemic hypoglycemia in infants is one of the most common causes of persistent hypoglycemia in infants. The knowledge of molecular defects leading to persistent hyperinsulinemic hypoglycemia in infants has been rapidly growing in recent years. According to the responsible genes, this ailment can be divided into five types. However, no molecular defect can be yet found in as many as 50% of the patients.