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Objective: To observe effects of different sulfonylurea compounds on expression of sulfonylurea receptor 2 (SUR2) in myocardium of the Goto-Kakizaki (GK) rats. Methods: Spontaneous diabetic GK rat models were divided into 6 groups: the diabetes model group, the Glibenclamide group, the Glipizide group, the Gliclazide group, the Glimepiride group and the positive control group(treated with insulin), with 12 rats in each group. A normal control group was also set up for comparison. The expression of SUR2 in myocardium of the GK rats was investigated by radioligand binding assay. SUR2 mRNA expression in the myocardial cells of rats was detected through reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Twelve weeks later, no significant difference was found in the SUR2 receptor density(Bmax)and affinity(Kd) between the sulfonylurea treated groups and the other 3 groups (P>0.05). There was no significant difference in SUR2 mRNA expression between the diabetic, insulin-treated diabetic and control groups(P>0.05). Cardiac SUR2 mRNA levels were not significantly different between sulfonylureas-treated diabetic and non-treated diabetic rats (P>0.05). Conclusion: The diabetes itself does not affect the sulfonylurea receptor(SUR2) expression in myocardial tissues. Sulfonylureas at treatment dosage have no effect on receptor expression of SUR2.
ABSTRACT
<p><b>OBJECTIVE</b>To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IK(ATP)) of rat ventricular myocytes.</p><p><b>METHODS</b>Isolated Langendorff perfused rat hearts were randomly assigned to five groups: (1) control group, (2) IPC group, (3) IPC + glibenclamide (GLB, 10 micromol/L) group, (4) IPC + glimepiride (GLM, 10 micromol/L) group, (5) IPC + gliclazide (GLC, 50 micromol/L) group. IPC was defined as 3 cycles of 5-minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded. And the sarcolemmal IK(ATP) of dissociated ventricular myocytes reperfused with 10 micromol/L GLB, 1 micromol/L GLM, and 1 micromol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition.</p><p><b>RESULTS</b>The infarct sizes of rat hearts in IPC (23.7% +/- 1.3%), IPC + GLM (24.6% +/- 1.0%), and IPC + GLC (33.1% +/- 1.3%) groups were all significantly smaller than that in control group (43.3% +/- 1.8%; P < 0.01, n = 6). The infarct size of rat hearts in IPC + GLB group (40.4% +/- 1.4%) was significantly larger than that in IPC group (P < 0.01, n=6). Under simulated ischemic condition, GLB (10 micromol/L) decreased IK(ATP) from 20.65 +/- 7.80 to 9.09 +/- 0.10 pA/pF (P < 0.01, n=6), GLM (1 micromol/L) did not significantly inhibit IK(ATP) (n=6), and GLC (1 micromol/L) decreased IK(ATP) from 16.73 +/- 0.97 to 11. 18 +/- 3.56 pA/pF (P < 0.05, n=6).</p><p><b>CONCLUSIONS</b>GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.</p>
Subject(s)
Animals , Male , Rats , Gliclazide , Pharmacology , Glyburide , Pharmacology , Heart , Ischemic Preconditioning , Rats, Sprague-Dawley , Sulfonylurea Compounds , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To observe the association between single nucleotide polymorphism (SNP) of peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC-1alpha ) gene and type 2 diabetes mellitus(T2DM).</p><p><b>METHODS</b>Four common SNPs of PGC-1alpha gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and then analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 69 T2DM pedigrees (310 individuals). Furthermore, the authors performed a case-control study to genotype Gly482Ser in 156 patients with T2DM and 111 normal glucose tolerance people without family history.</p><p><b>RESULTS</b>(1)There were no positive results in four variances in TDT-STDT analysis(P> 0.05). (2)The Gly482Ser exhibited a significant difference between the two groups. GA genotype carriers were at increased risk for T2DM (OR=1.85), and there was statistically significant difference in the allele frequency between the case and control groups(P=0.046). (3) The subjects with GG genotype at position Gly482Ser had a higher HDL-C and lower LDL-C and TG levels when compared against those with GA+AA genotype in the control group without family history(P=0.043,lzP=0.046, P=0.037 respectively).</p><p><b>CONCLUSION</b>This study suggested that the PGC-1alpha gene might be implicated in the pathogenesis of T2DM. But the studied SNPs in PGC-1alpha gene may not be major susceptibility ones of T2DM mellitus in Han people of Shanghai.</p>