BACKGROUNDThe Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between single-nucleotide polymorphisms (SNPs) in this gene and type 2 diabetes in the Chinese Han population.

METHODSWe selected 23 probands with a type 2 diabetic pedigree whose family members' average onset age was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m(2) and all of them were insulin-resistant (the fasting insulin level > 100 pmol/L or 16 µIU/ml). The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands. SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study. We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group. All these subjects were genotyped. A Snapshot Technology Platform (Applied Biosystems) was used for genotyping.

RESULTSThe Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T > C and 13007939G > T. 13010323T > C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G > T was in the 3'-untranslated region (UTR) of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Genbank. In the case-control study with 742 patients and 743 controls, there was no significant difference between the two groups for the allele frequency of rs2304186 (odd ratio: 0.96, 95% confidence interval: 0.82 - 1.12, P = 0.597).

CONCLUSIONSThe Akt2 gene is not a major cause of diabetes in a non-obese Chinese Han population characterized by insulin resistance. There is no significant relationship between rs2304186 and type 2 diabetes in the Chinese Han population.

Adult ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-akt ; genetics

OBJECTIVETo study the effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption for analyzing its underlying mechanism in the treatment of coronary heart disease.

METHODA total of 20 dogs anesthetized with pentobarbital sodium (30 mg x kg(-1), i.v.) were evenly randomized into control group, low-dose Gadol (LDG) group, high-dose Gadol (HDG) group and Herbesser Injection group. The blood flow volume (BFV) of the left coronary artery and cardiac output (CO), left ventricular pressure (LVP), maximum ascending rate (dp/dtmax) of LVP, mean arterial pressure (MAP) of the femoral artery, oxygen contents of the coronary artery and coronary vein (venous sinus), oxygen consumption index (OCI), cardiac index (CI), coronary artery resistance (CAR) and total peripheral resistance (TPR) as well as oxygen utilization rate (OUR) were detected respectively.

RESULTAfter venous injection of Gadol, CAR, MAP, TPR, OCI, myocardial oxygen consumption and heart rate lowered significantly (P < 0.05-0.01), while BFV and blood oxygen content of the venous sinus increased considerably (P < 0.05-0.01) in comparison with pre-injection. No significant differences were found in LVP and myocardial contractivity between control group and LDG, and between control and HDG groups respectively.

CONCLUSIONIt showed dilation of the coronary artery and reduction of the cardiac afterload after injection of Gadol. Besides, CO and stroke volume increased considerably and the cardiac effective work was raised without any significant simultaneous increase of both myocardial contractility and LVP. A decrease in the myocardial oxygen consumption and reduction of OCI indicates an improvement of the oxygen supply of the myocardium, and a favorable regulation of the compliance of the cardiac vessels. As a result, the cardiovascular performance was ameliorated. The abovementioned improvement of these indexes may contribute to the therapeutic effect of Gadol in the treatment of coronary heart disease in clinic.

Animals ; Blood Pressure ; drug effects ; Cardiac Output ; drug effects ; Dogs ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Injections, Intravenous ; Male ; Myocardium ; metabolism ; Oxygen ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rhodiola ; chemistry ; Vascular Resistance ; drug effects