The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with C...The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.展开更多
Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations...Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations and polymorphisms were detected in nine patients withacan-thosis nigricans (AN) and their first degree relatives in exon 17 and 20 of InsR gene. Thepolymorphisms and mutations were confirmed by DNA direct sequencing. Results: Fourteen variant SSCPpat-terns were detected. Direct sequencing revealed seven point mutations and six silentpolymorphisms. Five of the mutations appeared not to be mentioned in the previous literature. Thesemutations were all located within the domain of tyrokinase in InsR. Conclusion: It seem to us thatalmost all the AN patients with severe insulin resistance in this study have mutations in InsRtyrokinase domain.展开更多
Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible eff...Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible effects of milrinone on glucose metabolism andinsulin sensitivity in conscious rats. Methods The catheterized nonstressed rats were administeredvarious doses of milrinone (1, 5, 25μmoL·kg^(-1)) and were compared with controls. Ahyperinsulinaemic-eugly-caemic clamp was established in counscious rats, andmilrinone(25μmoL·kg^(-1)) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 minduring hyperinsulinaemic-euglycaemic clamping. Glucose turnover was determind with by gaschromatograph mass spectrometer (GC-MS). Results After dosing, plasma FFA levels in 3 milrinonegroups significantly increased, compared with the controls and before dosing. The percentages ofelevation of FFA by the different milrinone doses were very similar, 50%, and 52% , 55% for 1, 5,and 25 μmoL·kg^(-1), repectively, at 2 min after dosing. Plasma insulin levels were significantlyelevated in the 5 and 25 μmoL·kg^(-1) groups, and the effect of milrione on glucose concentrationwas detectable only in 25μmoL·kg^(-1) group. During hyperinsulinaemic clamping, there weresignificant increase, in plasma FFA (from 173 +- 15 to 634 +- 87μmoL·kg^(-1)) and hepatic glucoseproduction (HGP), and a significant decrease in glucose infusion rates (GIR) to about 21% and aslight increase in plasma insulin after milrinone treatment. Conclusion Milrinone impaires theability of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization inperipheral tissue. Therefore, milrinone administration may induce an acute insulin resistance invivo.展开更多
基金the Chinese High Tech Programs (863) from the Ministry of Science and Technology (No. 2002BA- 711A08)the National Natural Science Foundation of China (No. 30671155, and 39993420)+1 种基金Grant FMU-RT002 of Program for Innovative Research Team in Science and Technology in Fujian Province Universitythe Science Foundation from the Depart-ment of Education of Fujian Province (No. JA05251, and JB06215).
文摘The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.
文摘Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations and polymorphisms were detected in nine patients withacan-thosis nigricans (AN) and their first degree relatives in exon 17 and 20 of InsR gene. Thepolymorphisms and mutations were confirmed by DNA direct sequencing. Results: Fourteen variant SSCPpat-terns were detected. Direct sequencing revealed seven point mutations and six silentpolymorphisms. Five of the mutations appeared not to be mentioned in the previous literature. Thesemutations were all located within the domain of tyrokinase in InsR. Conclusion: It seem to us thatalmost all the AN patients with severe insulin resistance in this study have mutations in InsRtyrokinase domain.
文摘Aim To investigate the effects of milrinone (a selective phosphodiesteraseIII inhibitor PDE_3 ) on insulin secretion, blood glucose, plasma free fatty acids (FFA) anddose-response relationship, and assess possible effects of milrinone on glucose metabolism andinsulin sensitivity in conscious rats. Methods The catheterized nonstressed rats were administeredvarious doses of milrinone (1, 5, 25μmoL·kg^(-1)) and were compared with controls. Ahyperinsulinaemic-eugly-caemic clamp was established in counscious rats, andmilrinone(25μmoL·kg^(-1)) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 minduring hyperinsulinaemic-euglycaemic clamping. Glucose turnover was determind with by gaschromatograph mass spectrometer (GC-MS). Results After dosing, plasma FFA levels in 3 milrinonegroups significantly increased, compared with the controls and before dosing. The percentages ofelevation of FFA by the different milrinone doses were very similar, 50%, and 52% , 55% for 1, 5,and 25 μmoL·kg^(-1), repectively, at 2 min after dosing. Plasma insulin levels were significantlyelevated in the 5 and 25 μmoL·kg^(-1) groups, and the effect of milrione on glucose concentrationwas detectable only in 25μmoL·kg^(-1) group. During hyperinsulinaemic clamping, there weresignificant increase, in plasma FFA (from 173 +- 15 to 634 +- 87μmoL·kg^(-1)) and hepatic glucoseproduction (HGP), and a significant decrease in glucose infusion rates (GIR) to about 21% and aslight increase in plasma insulin after milrinone treatment. Conclusion Milrinone impaires theability of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization inperipheral tissue. Therefore, milrinone administration may induce an acute insulin resistance invivo.
