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Glucagon-like peptide-1 agonists:Role of the gut in hypoglycemia unawareness,and the rationale in type 1 diabetes
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作者 Hyder O Mirghani 《World Journal of Diabetes》 SCIE 2024年第11期2167-2172,共6页
Type 1 diabetes is increasing and the majority of patients have poor glycemic control.Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hyp... Type 1 diabetes is increasing and the majority of patients have poor glycemic control.Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 diabetes.Type 1 diabetes shares some pathophysiology with type 2 diabetes,and an overlap has been reported.The above observation created great interest in glucagon-like peptide-1 receptor agonists(GLP-1)as adjuvants for type 1 diabetes.Previous trials confirmed the positive influence of GLP-1 agonists onβcell function.However,hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists.Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut.Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption.This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes,particularly focusing on their impact on glycemic control,weight management,and glucagon dysregulation.We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions. 展开更多
关键词 glucagon-like peptide-1 receptor agonists glucagon response Hypoglycemia unawareness GUT Type 1 diabetes
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Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease:Opportunities and challenges
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作者 Chencheng Xie Naim Alkhouri Mohamed A Elfeki 《World Journal of Hepatology》 2024年第5期731-750,共20页
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health... Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 diabetes.Due to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is needed.Incretin receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD treatment.This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor agonists.Incretins and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose tissue.Thus,these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis.Importantly,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic inflammation.There are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in detail.Additionally,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions. 展开更多
关键词 Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis glucagon-like peptide-1 Glucose-dependent inulinotropic polypeptide glucagon INCRETIN Receptor agonist
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A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease
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作者 Jiaqian Chen Hongyan Wu 《Journal of Biosciences and Medicines》 2024年第3期16-24,共9页
Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that we... Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications. 展开更多
关键词 glucagon-Like Peptide 1 Receptor Agonists Nonalcoholic Fatty Liver Disease Type 2 Diabetes Mellitus
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Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion
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作者 Yu-Qi Li Lu-Yang Zhang +5 位作者 Yu-Chi Zhao Fang Xu Zhi-Yong Hu Qi-Hao Wu Wen-Hao Li Ya-Nuo Li 《World Journal of Diabetes》 SCIE 2023年第11期1643-1658,共16页
BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a redu... BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT. 展开更多
关键词 Vascular endothelial growth factor B Insulin-mediated glucagon secretion PREDIABETES Impaired glucose tolerance
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Type-2 Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor toward Predicting Possible Association
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作者 Nabaa Kamal Alshafei Intisar Hassan Saeed Mona Abdelrahman Mohamed Khaier 《Computational Molecular Bioscience》 2023年第3期48-62,共15页
Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduct... Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target. 展开更多
关键词 glucagon-Like Peptide-1 Receptor Single Nucleotide Polymorphism Insilico Analysis Non Synonymous SNP SIFT Polyphen-2 GeneMANIA
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Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus 被引量:5
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作者 Vishal J Patel Amit A Joharapurkar +6 位作者 Samadhan G Kshirsagar Brijesh K Sutariya Maulik S Patel Hiren M Patel Dheerendra K Pandey Rajesh H Bahekar Mukul R Jain 《World Journal of Diabetes》 SCIE CAS 2018年第6期80-91,共12页
AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintr... AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintreated high-fat diet fed C57 BL/6 J mice and diabeticC57 BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocintreated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes(SREBP-1 C, FAS, and SCD-1) was decreased, and expression of genes involved in β-oxidation(CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-?. Coagonist treatment reduced expression of inflammatory(TNF-α, MCP-1, and MMP-9) and pro-fibrotic(TGF-β, COL1 A1, and α-SMA) genes and also improved histological derangement in renal tissue.CONCLUSION Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia. 展开更多
关键词 Coagonist glucagon RENAL DYSFUNCTION glucagon-like peptide-1 INSULIN sensitivity
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Mutated recombinant human glucagon-like peptide-1 induces differentiation of PC12 cells 被引量:1
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作者 Jin Wu Lan Zhang +3 位作者 Zhongwei Sun Gang Huang Jing Huang Bing Mei 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第6期457-461,共5页
Glucagon-like peptide-1 (GLP-1) and its long-acting analogues have neuroprotective and neurotrophic properties and are emerging as potential treatments for neurodegenerative diseases. Its short half-life has limited... Glucagon-like peptide-1 (GLP-1) and its long-acting analogues have neuroprotective and neurotrophic properties and are emerging as potential treatments for neurodegenerative diseases. Its short half-life has limited the application of GLP-1 in the clinic. We generated a mutated form of human GLP-1 (mGLP-1) using site-directed mutagenesis and gene recombination techniques, and found that these modifications significantly prolonged the biological half-life of GLP-1 compared with native GLP-1 (nGLP-1). This study investigated the role of mGLP-1 on inducing PC12 cell differentiation, mGLP-1 induced PC12 cell differentiation with neurite outgrowth and increased the expression of growth-associated protein-43 and neuronal class III I^-tubulin, and significantly increased cyclic adenosine monophosphate level. No significant difference was found between mGLP-1 and nGLP-I. The results indicate that mGLP-1 activates the GLP-1 receptor, induces PC12 cell differentiation, and has neurotrophic effects. 展开更多
关键词 glucagon-like peptide-1 mutated glucagon-like peptide-1 DIFFERENTIATION PC12 cells
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Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome
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作者 Helen C Miller Mark Kidd +6 位作者 Irvin M Modlin Patrizia Cohen Roberto Dina Panagiotis Drymousis Panagiotis Vlavianos Günter Klöppel Andrea Frilling 《World Journal of Gastrointestinal Surgery》 2015年第4期60-66,共7页
Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity... Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity within the panel of non-syndromic disorders associated with hyperglucagonemia. This case report describes a 36-year-old female with a 10 years history of nonspecific abdominal pain. No underlying cause was evident despite extensive diagnostic work-up. More recently she was diagnosed with gall bladder stones. Abdominal ultrasound, computerised tomography and magnetic resonance imaging revealed no pathologic findings apart from cholelithiasis. Endoscopic ultrasound revealed a 5.5 mm pancreatic lesion. Fine needle aspiration showed cells focally expressing chromogranin, suggestive but not diagnostic of a low grade neuroendocrine tumor. Octreo Scan was negative. Serum glucagon was elevated to 66 pmol/L(normal: 0-50 pmol/L). Other gut hormones, chromogranin A and chromogranin B were normal. Cholecystectomy and enucleation of the pancreatic lesion were undertaken. Postoperatively, abdominal symptoms resolved and serum glucagon dropped to 7 pmol/L. Although H and E staining confirmed normal pancreatic tissue, immunohistochemistry was initially thought to be suggestive of alpha cell hyperplasia. A count of glucagon positive cells from 5 islets, compared to 5 islets from 5 normal pancreata indicated that islet size and glucagon cell ratios were increased, however still within the wide range of normal physiological findings. Glucagon receptor gene(GCGR) sequencing revealed a heterozygous deletion,K349_G359del and 4 missense mutations. This case may potentially represent a progenitor stage of glucagon cell adenomatosis with hyperglucagonemia in the absence of glucagonoma syndrome. The identification of novel GCGR mutations suggests that these may represent the underlying cause of this condition. 展开更多
关键词 Hyperglucagonemia glucagon receptorgene MUTATION Adenomatosis PANCREAS
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84例NIDDM辨证分型与IR Glucagon的关系 被引量:38
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作者 陆灏 丁学屏 蔡淦 《辽宁中医杂志》 CAS 北大核心 1998年第9期387-389,共3页
非胰岛素依赖型糖尿病(NIDDM)的病因目前尚不十分清楚,近年的研究表明,胰岛素抵抗(Insulinresistance,IR)、胰升糖素(Glucagon)分泌异常与NIDDM的发生、发展密切相关。笔者观察了84例... 非胰岛素依赖型糖尿病(NIDDM)的病因目前尚不十分清楚,近年的研究表明,胰岛素抵抗(Insulinresistance,IR)、胰升糖素(Glucagon)分泌异常与NIDDM的发生、发展密切相关。笔者观察了84例NIDDM患者临床辨证分型的情况及其与胰岛素抵抗、胰升糖素分泌异常的关系,并与正常组作了对比。结果表明:①气阴两虚型是NIDDM的常见证型。阴虚热盛型、气阴两虚型与阴阳两虚型均存在胰岛素抵抗和胰升糖素分泌异常,但各证型在程度上存在不同,提示各证型有着不同的病理生理特点。②对气阴两虚型的进一步观察证实,即使是同一证型,由于兼挟证的不同,其病理生理改变亦存在不同。气阴两虚兼燥热偏盛型其胰岛素抵抗、胰岛素分泌缺陷和胰升糖素分泌异常均较气阴两虚非燥热偏盛型更为明显。提示燥热偏盛与上述三者的改变有一定的联系。 展开更多
关键词 糖尿病 辨证分型 胰岛素抵抗 胰升糖素 NIDDM
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Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice 被引量:14
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作者 Takaya Yamamoto Yukiomi Nakade +7 位作者 Taeko Yamauchi Yuji Kobayashi Norimitsu Ishii Tomohiko Ohashi Kiyoaki Ito Ken Sato Yoshitaka Fukuzawa Masashi Yoneda 《World Journal of Gastroenterology》 SCIE CAS 2016年第8期2512-2523,共12页
AIM: To investigate whether a glucagon-like peptide-1(GLP-1) analogue inhibits nonalcoholic steatohepatitis(NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-defic... AIM: To investigate whether a glucagon-like peptide-1(GLP-1) analogue inhibits nonalcoholic steatohepatitis(NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet(MCD) along with exendin-4(20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice(non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride(TG) and free fatty acid(FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry.RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fattyacid transport protein 4(FATP4), a hepatic FFA influxrelated gene; macrophage recruitment; and the level of malondialdehyde(MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c(SREBP-1c) m RNA(lipogenesis-related gene) and acyl-coenzyme A oxidase 1(ACOX1) m RNA(β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein m RNA(a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 m RNA level. CONCLUSION: These results suggest that GLP-1 inhibits hepatic steatosis and inflammation through the inhibition of hepatic FFA influx and oxidative stress in a non-obese NASH model. 展开更多
关键词 glucagon like peptide-1 NONALCOHOLIC STEATOHEPATITIS KUPFFER cells Free FATTY acid Oxidative stress
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Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation 被引量:25
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作者 Xing-Chun Wang Aaron M Gusdon +1 位作者 Huan Liu Shen Qu 《World Journal of Gastroenterology》 SCIE CAS 2014年第40期14821-14830,共10页
Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They f... Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. 展开更多
关键词 glucagon-like peptide-1 receptor agonists Liver function Fat content Non-alcoholic fatty liver disease INFLAMMATION
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Effects of glucagon-like peptide-1 receptor agonists on renal function 被引量:9
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作者 Theodosios D Filippatos Moses S Elisaf 《World Journal of Diabetes》 SCIE CAS 2013年第5期190-201,共12页
Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of c... Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney injury.The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney injury.Based on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease.Liraglutide is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic impairment.There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect.Additionally,there is evidence that GLP-1 receptor agonists influence water and electrolyte balance.These effects may represent new ways to improve or even prevent diabetic nephropathy. 展开更多
关键词 glucagon-like PEPTIDE 1 glucagon-like PEPTIDE 1 receptor agonists EXENATIDE LIRAGLUTIDE Kidney Renal impairment Diabetic nephropathy Electrolytes
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EFFECTS OF GLUCAGON ON ISLET β CELL FUNCTION IN PATIENTS WITH DIABETES MELLITUS 被引量:5
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作者 Tong Wang Xin-hua Xiao Wen-hui Li Heng Wang Qi Sun Tao Yuan Guo-hua Yang 《Chinese Medical Sciences Journal》 CAS CSCD 2008年第2期117-120,共4页
Objective To evaluate islet β cell response to intravenous glucagon ( a non-glucose secretagogue) stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes (T1 D) and 131 patients with typ... Objective To evaluate islet β cell response to intravenous glucagon ( a non-glucose secretagogue) stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes (T1 D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ). In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ). The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups ( r = 0.76, P 〈 0.05 ). Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus. 展开更多
关键词 glucagon diabetes mellitus C-PEPTIDE islet β cell function
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Effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats 被引量:2
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作者 WU ZhiYong, ZHANG XiaoJie, JIAO Zhe, CHEN ZhiPing and KUANG YaoLing 《World Journal of Gastroenterology》 SCIE CAS CSCD 1997年第4期20-22,共3页
IM To investigate the effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats.METHODS Twentyeight male SpragueDawley rats were divided into two groups: intrahe... IM To investigate the effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats.METHODS Twentyeight male SpragueDawley rats were divided into two groups: intrahepatic portal hypertension (IHPH, n=14) by injection of CCl4 and prehepatic portal hypertension (PHPH, n=14) by stenosis of the portal vein. Animals of each group were divided into two subgroups: injection of octreotide and injection of normal saline. Seven agematched normal rats served as controls. The mean systemic arterial pressure (MSAP) and free portal venous pressure (FPP) were measured. The splanchnic blood flow was detected by injection of toad blood red cell labelled with 51Cr and 125I·T3. The concentration of plasma glucagon was determined by radioimmunoassay.RESULTS Octreotide significantly decreased both the splanchnic blood flow and FPP in portal hypertensive rats, and markedly increased splanchnic vascular and portal venous resistance. Octreotide did not significantly lower the plasma glucagon levels in both the peripheral and the portal veins.CONCLUSION The decreased splanchnic blood flow induced by octreotide in portal hypertensive rats results mainly from direct vasoconstriction but less from decreased plasma glucagon level. 展开更多
关键词 PORTAL hypertension octreotide glucagon SPLANCHNIC HEMODYNAMICS SOMATOSTATIN ANALOG
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Glucagon-like peptide-1 protects against cardiac microvascular endothelial cells injured by high glucose 被引量:11
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作者 Guang-Hao Ge Hong-Jie Dou +5 位作者 Shuan-Suo Yang Jiang-Wei Ma Wen-Bo Cheng Zeng-Yong Qiao Yue-Mei Hou Wei-Yi Fang 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2015年第1期73-78,共6页
Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay k... Objective:To investigate the protective effect of glucagon-like peptid-1(GLP-l) against cardiac microvascular endothelial cell(GTFCs) injured by high glucose.Methods:CMECs were isolated and cultured.Superoxide assay kit and dihydroethidine(DHE) staining were used to assess oxidative stress.TENEL staining and caspase 3 expression were used to assess the apoptosis of CMECs.H89 was used to inhibit eAMP/PKA pathway:fasudil was used to inhibit Rho/ROCK pathway.The protein expressions of Rho.ROCK uere examined by Western blol analysis.lesults:High glucose increased the production of ROS.the activity of NADPH.the apoptosis rate and the expression level of Rho/ROCK in CMECs.while GLP- 1 decreased high glucose-induced ROS production.the NADPH activity and the apoptosis rate and the expression level of Rho/ROCK in CMECs,the difference were statistically significant(P<0.05).Conclusions:GLP-1 could protect the cardiac microvessels against oxidative stress and apoptosis.The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-dependent manner,resulting in a subsequent decrease in the expression of NADPH oxidase. 展开更多
关键词 glucagon-like peptid-1 Cardiac MICROVASCULAR ENDOTHELIAL cell ROS Rho/ROCK
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玉米肽和有氧运动对肥胖大鼠血浆Glucagon、MCP-1、PP和PYY水平的影响 被引量:3
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作者 李翔 史仍飞 娄淑杰 《实验动物与比较医学》 CAS 2014年第3期214-218,共5页
目的 通过观察玉米肽和有氧运动对肥胖大鼠血浆内胰高血糖素(Glucagon)、单核细胞趋化蛋白-1 (monocyte chemoattractant protein-1,MCP-1)、胰多肽(Pancreatic polypeptide,PP)和酪酪肽(Peptide YY,PYY)水平的影响,探讨其减控... 目的 通过观察玉米肽和有氧运动对肥胖大鼠血浆内胰高血糖素(Glucagon)、单核细胞趋化蛋白-1 (monocyte chemoattractant protein-1,MCP-1)、胰多肽(Pancreatic polypeptide,PP)和酪酪肽(Peptide YY,PYY)水平的影响,探讨其减控大鼠体质量的可能激素相关机制.方法 雄性SD大鼠150只,随机选取15只作为普通饲料组(C组),给予普通饲料,其余135只给予高脂饲料以建肥胖模型.8周后将40只雄性肥胖大鼠随机分为肥胖对照组(OC组)、酪蛋白组(Cas组)、玉米肽组(CP组)、运动组(OE组)和玉米肽运动组(OEC组),其中OE组和OEC组进行4周的有氧运动.使用ELISA方法检测血浆中Glucagon、MCP-1、PP和PYY水平.结果 建模成功后经过4周干预,OC组大鼠体质量显著高于C组,OE组和OEC组大鼠体质量与OC组相比显著降低.OC组大鼠血Glucagon水平与C组无显著差异,CP组大鼠血Glucagon水平与OC组相比显著降低.OC组大鼠血MCP-1水平显著高于C组,CP组、OE组和OEC组与OC组大鼠血MCP-1水平相比显著降低.OC组大鼠血PYY水平均显著低于C组,OEC组大鼠血PYY水平显著高于OC组和CP组;各组大鼠间血PP水平均无显著性差异.结论 单纯服用玉米肽可以降低肥胖大鼠血Glucagon和MCP-1水平.玉米肽结合有氧运动可降低肥胖大鼠体质量以及血液内的MCP-1水平,并提高肥胖大鼠血液内PYY水平. 展开更多
关键词 玉米肽 有氧运动 胰高血糖素 单核细胞趋化蛋白-1(MCP-1) 胰多肽(PP) 酪酪肽(PPY)
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Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats 被引量:5
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作者 Jun Chen Jia-Tian Dong +3 位作者 Xiao-Jing Li Ye Gu Zhi-Jian Cheng Yuan-Kun Cai 《World Journal of Gastroenterology》 SCIE CAS 2015年第2期484-490,共7页
AIM: To observe the protective effect of glucagon-like peptide-2(GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect.MET... AIM: To observe the protective effect of glucagon-like peptide-2(GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect.METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase(ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14 th day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A(Ig A) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group.RESULTS: In the rat model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced Ig A expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group(P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group(P < 0.01).CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal Ig A and reduced bilirubin and endotoxin. 展开更多
关键词 INTESTINAL MUCOSAL BARRIER glucagon-likepeptide-2
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Effects of Electroacupuncture at Weiwanxiashu and Zusanli Points on Blood Glucose and Plasma Pancreatic Glucagon Contents in Diabetic Rabbits 被引量:2
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作者 曾志勇 李永义 王友京 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2002年第2期134-136,共3页
The Effects of electroacupuncture (EA) at Weiwanxiashu (EX-B3) and Zusanli (ST 36) points on blood glucose (BG) and plasma pancreatic glucagon (PG) contents were dynamically observed in diabetic rabbits induced by All... The Effects of electroacupuncture (EA) at Weiwanxiashu (EX-B3) and Zusanli (ST 36) points on blood glucose (BG) and plasma pancreatic glucagon (PG) contents were dynamically observed in diabetic rabbits induced by Alloxan. It is found that acupuncture at Weiwanxiashu point can significantly lower the BG content and inhibit release of PG; no significant changes in BG and PG are found when acupuncture is given at Zusanli (ST 36) point alone, however BG and PG contents decrease more obviously when acupuncture employed at both Zusanli and Weiwanxiashu, suggesting that Zusanli has a marked synergetic action with Weiwanxiashu. 展开更多
关键词 ELECTROACUPUNCTURE Acupuncture Points Animals Blood Glucose Diabetes Mellitus Experimental Female glucagon Male RABBITS
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Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity 被引量:2
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作者 Ananthi Anandhakrishnan Márta Korbonits 《World Journal of Diabetes》 SCIE CAS 2016年第20期572-598,共27页
Though the pathophysiology of clinical obesity is un-doubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1(GLP-1) signalling. Clinical studies as... Though the pathophysiology of clinical obesity is un-doubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1(GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose(3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed antiobesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and longterm weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need. 展开更多
关键词 OBESITY pathophysiology glucagon-like PEPTIDE 1 analogues glucagon-like PEPTIDE 1 CLINICAL OBESITY
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Effect of Acupuncture on Plasmic Levels of Insulin,Glucagon and Hypercoagulability in NIDDM Complicated by Acute Cerebral Infarction 被引量:1
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作者 谌剑飞 李创鹏 +2 位作者 丁萍 马雅玲 毛树章 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2001年第4期267-269,共3页
Twenty-one cases of acute cerebral infarction secondary to NIDDM were treated with acupuncture and conventional therapy, and compared with 16 cases treated with conventional therapy alone. The results showed that acup... Twenty-one cases of acute cerebral infarction secondary to NIDDM were treated with acupuncture and conventional therapy, and compared with 16 cases treated with conventional therapy alone. The results showed that acupuncture was more effective in reducing insulin and glucagon levels (P 展开更多
关键词 Acupuncture Therapy Cerebral Infarction Diabetes Mellitus Type 2 Female FIBRINOGEN glucagon Humans INSULIN Male Middle Aged Platelet Aggregation
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