OBJECTIVE: To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. METHODS: Sample...OBJECTIVE: To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. METHODS: Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700-(+)4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. RESULTS: Two amino acid variations [GGG-->AGG (G971 R) and CCT-->TCT (P1079 S)] and 3 silent mutations [GAT-->GAC(D422D), CCA-->CCC(P737 P) and GCA-->GCG (A804 A)] were identified, among which the CCA-->CCC(P737 P) and CCT-->TCT(P1079S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA-->GCG(A804A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, chi 2 = 18.42, P GCG (A804A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, chi 2 = 8.84, P 0.05). CONCLUSION: These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM.展开更多
BACKGROUND Perianal fistulae are either primary(idiopathic)or secondary[commonly associated with Crohn’s disease,(CD)].It is assumed,although not proven,that the pathophysiology differs.AIM To systematically compare ...BACKGROUND Perianal fistulae are either primary(idiopathic)or secondary[commonly associated with Crohn’s disease,(CD)].It is assumed,although not proven,that the pathophysiology differs.AIM To systematically compare the clinical phenotypes,cytokine and phosphoprotein profiles of idiopathic and CD-related perianal fistulae.METHODS Sixty-one patients undergoing surgery for perianal fistula were prospectively recruited(48 idiopathic,13 CD)into a cohort study.Clinical data,including the Perineal Disease Activity Index(PDAI)and EQ-5D-5L were collected.Biopsies of the fistula tract,granulation tissue,internal opening mucosa and rectal mucosa were obtained at surgery.Concentrations of 30 cytokines and 39 phosphoproteins were measured in each biopsy using a magnetic bead multiplexing instrument and a chemiluminescent antibody array respectively.Over 12000 clinical and 23500 laboratory measurements were made.RESULTS The PDAI was significantly higher(indicating more active disease)in the CD group with a mean difference of 2.40(95%CI:0.52-4.28,P=0.01).Complex pathoanatomy was more prevalent in the CD group,namely more multiple fistulae,supralevator extensions,collections and rectal thickening.The IL-12p70 concentration at the internal opening specimen site was significantly higher(median difference 19.7 pg/mL,99%CI:0.2-40.4,P=0.008)and the IL-1RA/IL-1βratio was significantly lower in the CD group at the internal opening specimen site(median difference 15.0,99%CI=0.4-50.5,P=0.008).However in the remaining 27 cytokines and all 39 of the phosphoproteins across the four biopsy sites,no significant differences were found between the groups.CONCLUSION CD-related perianal fistulae are more clinically severe and anatomically complex than idiopathic perianal fistulae.However,overall there are no major differences in cytokine and phosphoprotein profiles.展开更多
Summary： The relationship between tyrosine phosphorylation （TP） and protein expression of insulin receptor （InsR） and insulin resistance （IR） in patients with gestational diabetes mellitus （GDM） was investiga...Summary： The relationship between tyrosine phosphorylation （TP） and protein expression of insulin receptor （InsR） and insulin resistance （IR） in patients with gestational diabetes mellitus （GDM） was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM （GDM group, n=22）, normal pregnant women （normal pregnancy group, n=22） and normal non-pregnant women （normal non-pregnant group, n=13）. Fasting plasma glucose （FPG） and fasting insulin （FINS） were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG （5.61±0.78 mmol/L）, FINS （15.42±5.13 mU/L） and Ho- meostasis model assessment-IR （HOMA-IR） （1.21±0.52） in GDM group were significantly higher than those in normal pregnancy group （4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively） （P〈0.01）. The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group （7.56±2.31 mU/L and 0.47±0.26 respectively） （P〈0.01）. There was no significant difference in the InsR expression level among the three groups （P〉0.05）. TP of InsR with insulin stimulation was significantly decreased in GDM group （0.20±0.05） as compared with normal pregnancy group （0.26±0.06） （P〈0.01）. TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group （0.31±0.06） （P〈0.01）. TP of InsR with insulin stimu- lation was negatively related with HOMA-IR in GDM group （r=-0.525, P〈0.01）. There was no correlation between the protein expression of InsR and HOMA-IR in GDM group （r=-0.236, P〉0.05）. It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.展开更多
文摘OBJECTIVE: To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. METHODS: Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700-(+)4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. RESULTS: Two amino acid variations [GGG-->AGG (G971 R) and CCT-->TCT (P1079 S)] and 3 silent mutations [GAT-->GAC(D422D), CCA-->CCC(P737 P) and GCA-->GCG (A804 A)] were identified, among which the CCA-->CCC(P737 P) and CCT-->TCT(P1079S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA-->GCG(A804A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, chi 2 = 18.42, P GCG (A804A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, chi 2 = 8.84, P 0.05). CONCLUSION: These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM.
基金Supported by Bowel and Cancer Research charity,No.MMBG1J3R
文摘BACKGROUND Perianal fistulae are either primary(idiopathic)or secondary[commonly associated with Crohn’s disease,(CD)].It is assumed,although not proven,that the pathophysiology differs.AIM To systematically compare the clinical phenotypes,cytokine and phosphoprotein profiles of idiopathic and CD-related perianal fistulae.METHODS Sixty-one patients undergoing surgery for perianal fistula were prospectively recruited(48 idiopathic,13 CD)into a cohort study.Clinical data,including the Perineal Disease Activity Index(PDAI)and EQ-5D-5L were collected.Biopsies of the fistula tract,granulation tissue,internal opening mucosa and rectal mucosa were obtained at surgery.Concentrations of 30 cytokines and 39 phosphoproteins were measured in each biopsy using a magnetic bead multiplexing instrument and a chemiluminescent antibody array respectively.Over 12000 clinical and 23500 laboratory measurements were made.RESULTS The PDAI was significantly higher(indicating more active disease)in the CD group with a mean difference of 2.40(95%CI:0.52-4.28,P=0.01).Complex pathoanatomy was more prevalent in the CD group,namely more multiple fistulae,supralevator extensions,collections and rectal thickening.The IL-12p70 concentration at the internal opening specimen site was significantly higher(median difference 19.7 pg/mL,99%CI:0.2-40.4,P=0.008)and the IL-1RA/IL-1βratio was significantly lower in the CD group at the internal opening specimen site(median difference 15.0,99%CI=0.4-50.5,P=0.008).However in the remaining 27 cytokines and all 39 of the phosphoproteins across the four biopsy sites,no significant differences were found between the groups.CONCLUSION CD-related perianal fistulae are more clinically severe and anatomically complex than idiopathic perianal fistulae.However,overall there are no major differences in cytokine and phosphoprotein profiles.
基金supported by the Doctoral Fund of ShandongProvince in China(No.2006BS03053)
文摘Summary： The relationship between tyrosine phosphorylation （TP） and protein expression of insulin receptor （InsR） and insulin resistance （IR） in patients with gestational diabetes mellitus （GDM） was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM （GDM group, n=22）, normal pregnant women （normal pregnancy group, n=22） and normal non-pregnant women （normal non-pregnant group, n=13）. Fasting plasma glucose （FPG） and fasting insulin （FINS） were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG （5.61±0.78 mmol/L）, FINS （15.42±5.13 mU/L） and Ho- meostasis model assessment-IR （HOMA-IR） （1.21±0.52） in GDM group were significantly higher than those in normal pregnancy group （4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively） （P〈0.01）. The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group （7.56±2.31 mU/L and 0.47±0.26 respectively） （P〈0.01）. There was no significant difference in the InsR expression level among the three groups （P〉0.05）. TP of InsR with insulin stimulation was significantly decreased in GDM group （0.20±0.05） as compared with normal pregnancy group （0.26±0.06） （P〈0.01）. TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group （0.31±0.06） （P〈0.01）. TP of InsR with insulin stimu- lation was negatively related with HOMA-IR in GDM group （r=-0.525, P〈0.01）. There was no correlation between the protein expression of InsR and HOMA-IR in GDM group （r=-0.236, P〉0.05）. It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.
