Application of sodium-glucose cotransporter 2 inhibitors in acute myocardial infarction / 中国临床药理学与治疗学

SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Correlation and protective effect of diabetes mellitus in aortic aneurysm disease / 国际外科学杂志

Diabetes mellitus is a metabolic disease characterized by hyperglycemia. It is found that the incidence and mortality of abdominal aortic aneurysm (AAA) in diabetes mellitus patients are lower than that in non-diabetes mellitus patients. This review will present the protective role of diabetes mellitus and its treatment on the aortic disease process, aiming to provide more support for the clinical treatment of AAA.

Role of energy synthesis disorders in pathogenesis of Alzheimer' s disease / 中国药理学通报

Alzheimer's disease is a neurodegenerative disease with multiple causes. Due to no effective drugs to reverse the progress of AD, many researchers in the world focus on the early pathological changes of AD in order to find the effective intervention for delaying the progress of AD. As an organ with high energy demand, brain is very sensitive to changes in fuel supply and energy alteration. Abnormal glucose metabolism and mitochondrial dysfunction are the important signs of brain aging and the main causes of bioenergetic deficits, which appear earlier than the characteristic pathological injuries of AD. So the disturbance of energy synthesis has been considered an early contributory e- vent to AD progression. In this article we review the study progress of energy synthesis disorder involved in the pathogenesis of AD base on cerebral blood flow, glucose uptake, utilization and the relative metabolic regulation in the brain.

A glucose-insulin-potassium solution improves glucose intake in hypoxic cardiomyocytes by a differential expression of glucose transporters in a metabolic syndrome model

Among the last consequences of metabolic syndrome are cardiovascular complications such as infarcts. The hypoxic heartswitches its lipid-based metabolism to carbohydrates, and a glucose-insulin-potassium (GIK) solution can be the metabolicsupport to protect the organ. Due to the physiology and cardiac risks associated with the metabolic syndrome, we studied theeffect of GIK solution during hypoxia in a metabolic syndrome model by observing the participation of glucose transporters(GLUTs). The metabolic syndrome characteristics were established by giving a 30% sucrose drinking solution to Wistar ratsfor 24 weeks. The GIK solution’s effect on myocyte glucose uptake during hypoxia and oxygenation was observed using acolorimetric method, and Western blot technique visualized the GLUT participation. Oxygenated control myocytes consumed1.7 ± 0.2 µg of glucose per gram of fresh tissue per hour using the GLUT1, and during hypoxia, they incorporated 41.1%more glucose by GLUT1 and GLUT4. The GIK solution improved glucose uptake in oxygenation by 70.5% through GLUT1.In hypoxia, the uptake was 21% more than the hypoxic control group and by both GLUTs too. Oxygenated metabolicsyndrome myocytes uptake was similar to control cells but achieved by both carriers in oxygenation and hypoxia. Also, theGIK solution had a better response in both oxygenation (113%) and hypoxia (71%). Despite the metabolic energy disorders ofthis syndrome, the GIK solution protects cardiomyocytes, in conditions of hypoxia, through the modulation of both GLUTs.So, this solution can be considered a useful resource during a heart attack in cases of metabolic syndrome.

Effects of polysaccharides from Ginkgo biloba on proliferation of 4T1 breast cancer cells and expression of GLUT family genes / 中国药理学通报

Aim To investigate the effects of polysac-charides from Ginkgo biloba on the proliferation, apop-tosis of mouse 4T1 breast cancer cells and the possible mechanism. Methods 4T1 cells in logarithmic growth phase were treated with polysaccharides from Ginkgo biloba of different concentrations. The effect of poly-saccharides from Ginkgo biloba on inhibition of prolif-eration and cytotoxicity of 4T1 cells was determined by MTT assay and trypan blue exclusion assay respective-ly. The apoptotic effect of polysaccharides from Ginkgo biloba on 4T1 cells was detected by DAPI staining. qRT-PCR experiments were carried out for the detec-tion of gene expressions of the glucose transporter fami-ly upon the treatment with the polysaccharides from Ginkgo biloba. Results Polysaccharides from either Ginkgo biloba leaf or Ginkgo biloba exocarp significant-ly inhibited the proliferation of 4T1 cells in a dose-and time-dependent manner. Moreover, with the increasing doses of polysaccharides, cell viability decreased, ac-companied by the increased cell cytotoxicity and apop-tosis. qRT-PCR results showed that polysaccharides from Ginkgo biloba significantly reduced glucose trans-porter 1 gene expression. Conclusions Polysaccha-rides from Ginkgo biloba can both inhibit 4T1 cell pro-liferation and induce cell apoptosis, and by regulating glucose transporter family gene expression, it interfered with cell energy metabolism, which infers that the effects of cell proliferation inhibition as well the apopto-sis induction might be due to the regulation of glucose transporter family gene expression.

Research progress of GLUT1 in urinary tumor / 医学研究生学报

Glucose transporters protein (GLUTs) is the main carrier of glucose transport in mammalian cells, in which GLUT1 is the most widely distributed in glucose transporter in vivo. Studies have shown that GLUT1 has abnormally high expression in urinary tract tumors such as renal cell carcinoma,prostate cancer,bladder cancer and nephroblastoma,cleading to increased intracellu-lar glucose uptake,which is closely related to tumor occurrence,evolution,invasion,prognosis and drug resistance. As a new target of tumor therapy,GLUT1 has attracted extensive attention. This review summarizes the recent advances on the expression of GLUT1 in tumor and its mechanism,which can provide a new perspective for the treatment and prognosis evaluation of tumor.

A glucose-centric perspective of hyperglycemia.

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (>200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and targets. Some are effective in slowing formation of glucose in intestines by inhibiting α–glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweeteners, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbA1c, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

Application of functional imaging in diagnosis of diabetes mellitus / 中华内分泌代谢杂志

In either type 1 or type 2 diabetes,there is significant loss of β cell mass.Understanding the changing of β cell mass in the course of diabetes would provide important information for diagnosis and treatment.Functional imaging like magnetic resonance imaging or positron emission tomography (PET) can provide safe and noninvasive detection of loss of β cell mass in the course of diabetes.Among them,radio-labelled imaging is the most sensitive imaging procedure of the β cell ; For dihydrotetrabenazine PET imaging aiming β cell mass,there has been some primary outcome.For the key factor causing type 2 diabetes,18 F-6-deoxy-6-fluoro-D-glucose (18F-6-FDG) PET imaging is an effective tracer to study the glucose transporting condition in vivo.Further development of functional imaging will be of great value in diagnosis and treatment of diabetes.

Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium (KATP) channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of KATP channels, insulin receptor beta-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that KATP-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on KATP channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

Transient ischemia and reperfusion induce the expression of glucose transporters GLUT1 and GLUT4 in rat myocardium / 医学研究生学报

Objective : To investigate the dynamic changes of the expression of GLUT1 mRNA and GLUT4 mRNA in rats myocardium with transient ischemia and reperfusion, and the relationship between the dynamic changes and the time during reperfusion. Methods : In rats, the left anterior descending coronary artery was occluded for 20 min followed by reperfusion for 4 hours, 1, 3 or 7 days as ischemia reperfusion model. The relative content of GLUT1 mRNA and GLUT4 mRNA in myocardium was detected by RT-PCR and gel electrophoresis imaging. Results: During myocardial post-ischemia and reperfusion, the levels of GLUT1 mRNA got up to the peak at 4th hour[ (0.666?0. 003 ) vs (0. 509?0.002) controls , P 0.05). Conclusion; Transient ischemia and reperfusion induce the expression of glucose transporters GLUT1 and GLUT4 genes in rat myocardi- um, which contribute to promote glucose utilization during ischemia, protect ischemic myocardium and improve functional recovery on reperfusion.