糖耐量低减的危害及其机制

糖耐量低减 (ＩＧＴ)是一组已有代谢异常并有可能向糖尿病 (ＤＭ )发展的病理生理过程的中间阶段 ,其诊断标准为口服 75 ｇ葡萄糖 (ＯＧＴＴ)后 2小时所测静脉血浆葡萄糖处于 7.8～ 11.1ｍｍｏｌ/Ｌ之间者。近年来的研究表明ＩＧＴ者不仅存在胰岛素分泌和作用的缺陷 ,具有发生 2型糖尿病的倾向 ,而且常与高胰岛素血症、脂代谢紊乱、肥胖等代谢异常综合征并存 ,具有高度发生心血管疾病的危险性。使ＩＧＴ者较糖耐量正常者有更高的病死率。因此充分认识ＩＧＴ的危害 ,并对其进行干预治疗 (包括健康的生活方式或必要时使用药物 ) ,对延缓和减少…     

Inhibition of gastric acid secretion by jejunal glucose and its relation to osmolality and glucose load

Intrajejunal infusion of hypertonic glucose and hypertonic saline inhibits pentagastrin-stimulated gastric acid secretion in man. This effect is generally ascribed to the hyperosmolality of the solutions. Five volunteers were given 50 g glucose in osmolar concentrations of 2700 mosmol/l and 900 mosmol/l, and five were given 25 g glucose in osmolar concentrations of 2700 mosmol/l and 300 mosmol/l. Control studies with intrajejunal infusion of physiologic saline were performed in all subjects. Median inhibition of gastric acid secretion was 91% after 50 g glucose and 47% after 25 g glucose and was unrelated to the osmolar concentration. These findings suggest that the acid-inhibitory effect of intrajejunally administered glucose is related to the glucose load and not to the osmolar concentration. Plasma responses of intact neurotensin, immunoreactivity, NH2-terminal neurotensin immunoreactivity, enteroglucagon, and gastric inhibitory polypeptide were all related to the amount of glucose given. Glucagon and somatostatin, both of which are potent inhibitors of gastric secretion, were not released by intrajejunally administered glucose.     

葡萄糖代谢异常相关认知障碍及防治

北京市西城区科技计划项目（2012JH29）     

Kidney: its impact on glucose homeostasis and hormonal regulation

According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although animal and in vitro studies have documented that the kidney is capable of gluconeogenesis, glucose production by the human kidney has been regarded as negligible. This knowledge is based on net balance measurements across the kidney. Recent studies combining isotopic and balance techniques have demonstrated that the human kidney is involved in the regulation of glucose homeostasis by making glucose via gluconeogenesis, taking up glucose from the circulation, and by reabsorbing glucose from the glomerular filtrate. The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the postabsorptive state. In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis actually increases by approximately 2-fold. Following meal ingestion, glucose utilization by the kidney increases. Increased glucose uptake into the kidney may be implicated in diabetic nephropathy. Normally each day, ～ 180 g of glucose is filtered by the kidneys; almost all of this is reabsorbed by means of sodium glucose cotransporter 2 (SGLT2), expressed in the proximal tubules. However, the capacity of SGLT2 to reabsorb glucose from the renal tubules is finite and when plasma glucose concentrations exceed a threshold, glucose begins to appear in the urine. Renal glucose release is stimulated by epinephrine and is inhibited by insulin. Handling of glucose by the kidney is altered in type 2 diabetes mellitus (T2DM): renal gluconeogenesis and renal glucose uptake are increased in both the postabsorptive and postprandial states, and renal glucose reabsorption is also increased Since renal glucose release is almost exclusively due to gluconeogenesis, it seems that the kidney is as important gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactae glutamine and glycerol.     

糖尿病及糖调节受损的诊断标准及其变迁

回顾了糖尿病诊断标准的产生背景、修改过程及依据,介绍了空腹血糖受损及糖耐量减低概念的提出及诊断切点的调整变化及这种变化所带来的益处。同时,比较了美国糖尿病学会与世界卫生组织糖尿病诊断标准的不同之处,指出目前糖尿病诊断中的不足之处。另外,糖化血红蛋白A1c可能成为糖尿病筛查和诊断的可靠指标。     

Effects of ingesting glucose and some of its polymers on serum glucose and insulin levels in men and women

Twelve men and 10 women were given maltodextrin (DE20) at various dose levels after an overnight fast. Similar studies were carried out with glucose, maltose and another maltodextrin (DE5). It was found that within each sex the serum glucose and insulin responses were not influenced by the physical form of glucose ingested over a 90-min period. However, the serum glucose response to glucose and to its polymers was found to be dose-dependent in the men but not in the women. The serum insulin response was dose-dependent in both sexes. At any glucose dose level the serum insulin response was approximately 40% greater in men compared to women.     

Carbohydrate and lipid oxidation in normal human subjects: its influence on glucose tolerance and insulin response to glucose

Two types of glucose tolerance tests (OGTT and 90-min glucose infusions) were carried out on 33 normal subjects in whom free fatty acid levels were either raised by neutral fat infusion or lowered by β-pyridyl carbinol infusion. With continuous measurement of O₂ consumption and of nonprotein respiratory quotient during these tests, it could be demonstrated that the fat infusion before glucose load was followed by an increased lipid oxidation and that carbohydrate oxidation was diminished. The glucose load (without fat infusion) induced a rapid increase of carbohydrate oxidation and a decrease of lipid oxidation. When FFA was raised, a glucose load was followed by increased carbohydrate oxidation less than was observed in cases where glucose only was given. Glucose tolerance was found to be depressed by the simultaneous administration of lipids, while insulin response to glucose load was significantly increased. These observations find support in the known inhibition of glucose oxidation induced by fatty acid oxidation. Glucose intolerance and insulin insensitivity appear to be a consequence of this mechanism. Decreased lipid oxidation, increased carbohydrate oxidation, improved glucose tolerance, and lower insulin response to glucose load with apparent “insulin hypersensitivity” was observed while lowering free fatty acid levels with a β-pyridyl carbinol infusion.     

不同糖代谢状态下大鼠肝X受体的表达及其对肝糖代谢的影响

目的 观察肝X受体(LXR)在不同糖代谢状态下肝内表达的变化情况及其对肝糖代谢酶磷酸烯醇式丙酮酸羧激酶(PEPCK)mRNA和葡萄糖激酶(GCK)mRNA表达的调节,阐明LXR信号通路对糖代谢的影响机制.方法 SD雄鼠36只分为正常对照组、糖尿病组、肥胖组和肥胖伴糖尿病组.测定各组大鼠的体重、血糖、胆固醇和甘油三酯.采用实时PCR检测各组大鼠肝脏LXR mRNA、PEPCK mRNA和GCK mRNA的表达情况,应用Western印迹测定肝脏LXR蛋白质的表达.结果 各实验组大鼠肝LXRmRNA表达均显著高于对照组(P＜0.05).Western印迹结果示各组LXR蛋白表达量和转录水平一致.与对照组和肥胖组相比,肥胖伴糖尿病组和糖尿病组肝PEPCK mRNA表达均明显上调,GCK mRNA均明显下调;与对照组相比,肥胖组PEPCKmRNA表达明显下降,GCKmRNA明显上升(均P＜0.05).结论 在非糖尿病阶段,LXR可能作为糖代谢的保护性受体,通过调节肝糖代谢酶,使血糖保持稳态.进入糖尿病阶段后,LXR的保护作用并不能逆转因胰岛素不足所致的糖代谢相关酶的异常改变,血糖不能恢复正常.

Abstract：

Objective To investigate the mechanism of liver X receptor(LXR)signal pathway in regulating glucose metabolism by observing the variety of LXR expression and its impacts on regulating the mRNA expression of PEPCK and GCK, the key enzyme of hepatic glucose metabolism in various glucose metabolic status in rats. Methods SD rats were chosen and divided into four groups:the CON group, the induced DM group, the OB group, and the induced OB+DM group. For each group of rats, body weight, blood glucose, serum triglycerides, and cholesterol were measured. Then the rats were sacrificed and the livers were collected and studied. Real-time PGR was used to measure the expressions of LXR mRNA, PEPCK mRNA, and GCK mRNA in the livers. Finally, the Western Blot assay was used to measure the liver LXR protein expression. Results The expression of LXR mRNA was significantly higher in DM,OB, and OB+DM groups than in CON group(P＜0.05).The Western blot results showed that the levels of protein were in accordance with the mRNA expression. Comparing to the CON and the OB groups, the PEPCK mRNA expression of the OB+DM and the DM groups was significantly higher, while the GCK mRNA expression of these two groups was significantly lower(P＜0.05). Comparing to the CON group, the PEPCK mRNA expression of the OB group was significantly lower, while the GCK mRNA expression of OB group was significantly higher(P＜0.05).Conclusions During non-diabetic phase, LXR could act as a protective receptor for glucose metabolism and keep glucose homeostasis by regulating the key enzymes of the hepatic glucose metabolism. While in the diabetic phase, the protective receptor LXR failed to reverse the change of the related enzymes caused by insulin deficiency, and finally the plasma glucose level was raised.     

胰高血糖素样肽-1及其类似物的降糖机制

Glucagon-like peptide-1 (GLP-1) is an insulin secretagogue that secreted by intestinal L-cells. After binding with its receptor, GLP-1 stimulates glucose-dependent insulin secretion, β-cell prolifera-tion and differentiation as well as inhibits its apeptosis, decelerates gastric emptying, improves insulin sensi-tivity of periphery tissue. The long-acting GLP-1 analogues decrease hyperglycemia safely without weight gain and hypoglycemia and protect the function of pancreatic islet beta-cell. Using GLP-1 analogues at early stages of the disease,impaired beta-cell function and possibly beta-cell mass appear to be reversible. These agents axe, therefore, considered new therapeutic agents for the treatment of patients with type 2 diabetes.     

胰高血糖素样肽-1及其类似物的降糖机制

Glucagon-like peptide-1 (GLP-1) is an insulin secretagogue that secreted by intestinal L-cells. After binding with its receptor, GLP-1 stimulates glucose-dependent insulin secretion, β-cell prolifera-tion and differentiation as well as inhibits its apeptosis, decelerates gastric emptying, improves insulin sensi-tivity of periphery tissue. The long-acting GLP-1 analogues decrease hyperglycemia safely without weight gain and hypoglycemia and protect the function of pancreatic islet beta-cell. Using GLP-1 analogues at early stages of the disease,impaired beta-cell function and possibly beta-cell mass appear to be reversible. These agents axe, therefore, considered new therapeutic agents for the treatment of patients with type 2 diabetes.     

要重视钙离子拮抗剂在代谢紊乱中的应用

长效钙拮抗剂(CCB)广泛用于治疗心绞痛、高血压、心律失常等疾病。近年来大型临床试验的结果为CCB在代谢紊乱患者中的应用提供了更充分的证据。高血压常合并脂代谢紊乱、糖代谢紊乱、胰岛素抵抗及高尿酸血症等多重代谢异常,然而CCB具有血管舒张、改善内皮功能、抗动脉粥样硬化、减少尿蛋白等作用。对这些代谢紊乱患者应用CCB会带来益处还是会增加风险?一直在不同领域(心血管及内分泌代谢研究领域)存在着疑虑。本文将着重探讨CCB在代谢紊乱中的应用。     

胰高血糖素样肽-1及其类似物的降糖机制

胰岛素为一具多种生物学效应的激素 ,在生理上保持营养物质代谢平衡 ,维持内环境恒定 ,调控细胞生长、增殖 ,保证正常的生长发育 ;在病理生理上 ,胰岛素分泌量过多或过少 ,对靶组织的敏感性加强或减弱都会造成病态 ,尤其是胰岛素抵抗及伴发的代谢综合征和 2型糖尿病已形成流行态势 ,严重危害中、老年人健康。胰岛素于 2 0世纪二十年代初问世 ,其生理作用的研究广泛而深入 ,但其确切的作用机制 ,在细胞、分子水平的生化过程多年不明。 5 0年后 ,1971年通过同位素标记的胰岛素与肝细胞膜制备物结合特性的研究 ,确定了胰岛素受体 (ＩＲ)的存在 …     

胰高血糖素样肽-1及其类似物的降糖机制

Glucagon-like peptide-1 (GLP-1) is an insulin secretagogue that secreted by intestinal L-cells. After binding with its receptor, GLP-1 stimulates glucose-dependent insulin secretion, β-cell prolifera-tion and differentiation as well as inhibits its apeptosis, decelerates gastric emptying, improves insulin sensi-tivity of periphery tissue. The long-acting GLP-1 analogues decrease hyperglycemia safely without weight gain and hypoglycemia and protect the function of pancreatic islet beta-cell. Using GLP-1 analogues at early stages of the disease,impaired beta-cell function and possibly beta-cell mass appear to be reversible. These agents axe, therefore, considered new therapeutic agents for the treatment of patients with type 2 diabetes.     

胰高血糖素样肽-1及其类似物的降糖机制

Glucagon-like peptide-1 (GLP-1) is an insulin secretagogue that secreted by intestinal L-cells. After binding with its receptor, GLP-1 stimulates glucose-dependent insulin secretion, β-cell prolifera-tion and differentiation as well as inhibits its apeptosis, decelerates gastric emptying, improves insulin sensi-tivity of periphery tissue. The long-acting GLP-1 analogues decrease hyperglycemia safely without weight gain and hypoglycemia and protect the function of pancreatic islet beta-cell. Using GLP-1 analogues at early stages of the disease,impaired beta-cell function and possibly beta-cell mass appear to be reversible. These agents axe, therefore, considered new therapeutic agents for the treatment of patients with type 2 diabetes.     

小檗碱对脂肪细胞葡萄糖转运的影响及其机制研究

目的 观察小檗碱对3T3-L1脂肪细胞葡萄糖转运的影响，并探讨其机制。方法 以葡萄糖氧化酶法检测细胞的葡萄糖消耗量，以2-脱氧-^3H-D-葡萄糖摄入法观察葡萄糖的转运率，以免疫共沉淀和蛋白免疫印迹检测蛋白激酶B(protein kinase B，Akt)活性，以Northern印迹检测c-Cbl相关蛋白(CAP)mRNA的表达。结果 0．1-200μmol／L小檗碱显著增加3T3-L1脂肪细胞的葡萄糖消耗，呈剂量依赖效应，其作用不需要胰岛素的存在；0．1～10μmol／L小檗碱显著增加脂肪细胞的葡萄糖转运，在其作用2h后，葡萄糖转运即显著增加，至12h时，其作用趋近最大；免疫共沉淀和蛋白免疫印迹结果显示，小檗碱并未增强Akt激酶活性；Northern印迹结果显示，小檗碱明显降低CAP mRNA的表达。结论 脂肪细胞是小檗碱的重要靶细胞，小檗碱显著增加脂肪细胞的葡萄糖转运和消耗，可能并非通过已知的胰岛素信号转导途径。     

胰高血糖素样肽-1及其类似物的降糖机制

Glucagon-like peptide-1 (GLP-1) is an insulin secretagogue that secreted by intestinal L-cells. After binding with its receptor, GLP-1 stimulates glucose-dependent insulin secretion, β-cell prolifera-tion and differentiation as well as inhibits its apeptosis, decelerates gastric emptying, improves insulin sensi-tivity of periphery tissue. The long-acting GLP-1 analogues decrease hyperglycemia safely without weight gain and hypoglycemia and protect the function of pancreatic islet beta-cell. Using GLP-1 analogues at early stages of the disease,impaired beta-cell function and possibly beta-cell mass appear to be reversible. These agents axe, therefore, considered new therapeutic agents for the treatment of patients with type 2 diabetes.     

胰高血糖素样肽-1及其类似物的降糖机制

胰高血糖素样肽-1(GLP-1)是由肠道L细胞分泌的肠促胰岛素,对调节机体葡萄糖稳态有重要作用.GLP-1与其受体结合后,促进葡萄糖依赖的胰岛素分泌、胰岛β细胞增殖和分化并抑制其凋亡、延迟胃排空、增加外周组织对胰岛素的敏感性,但不引起体重增加和低血糖,从而保护了胰岛β细胞功能.在疾病早期应用此类药物后,受损的β细胞功能和β细胞数量有逆转的可能.GLP-1及其类似物必将成为治疗糖尿病的一个新亮点.