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Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease 被引量:1
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作者 Maurizio Soresi Lydia Giannitrapani 《World Journal of Gastroenterology》 SCIE CAS 2024年第30期3541-3547,共7页
In this editorial,we comment on Yin et al’s recently published Letter to the editor.In particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combinat... In this editorial,we comment on Yin et al’s recently published Letter to the editor.In particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic pathology.It is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive damage.Several clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve fibrosis.Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease.In particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than monotherapy.Therefore,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy. 展开更多
关键词 Non-alcoholic fatty liver disease glucagon-like peptide 1 Semaglutide Liver fibrosis Therapy
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Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain
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作者 Yolanda Diz-Chaves Zainab Maastor +3 位作者 Carlos Spuch José Antonio Lamas Lucas C.González-Matías Federico Mallo 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1671-1677,共7页
The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activati... The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine. 展开更多
关键词 ASTROCYTES BRAIN glucagon-like peptide 1 receptor INFLAMMATION MICROGLIA
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Glucagon-like peptide 1 receptor agonist:A potential game changer for cholangiocarcinoma
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作者 Ronnakrit Trakoonsenathong Ching-Feng Chiu Charupong Saengboonmee 《World Journal of Gastroenterology》 SCIE CAS 2024年第34期3862-3867,共6页
Glucagon-like peptide-1 receptor(GLP-1R)agonist,a subgroup of incretin-based anti-diabetic therapies,is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protectio... Glucagon-like peptide-1 receptor(GLP-1R)agonist,a subgroup of incretin-based anti-diabetic therapies,is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection.Contrarily,concerns have been raised about GLP-1R agonists increasing the risk of particular cancers.Recently,several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma(CCA).The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA.Later studies,however,showed a null effect of incretinbased therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist.Mechanistically,glucagon-like peptide 1 receptor is multifunctional,including promoting cell growth.High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro.Unexpectedly,the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms.Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo,leading to the inhibition of CCA tumor growth.This editorial reviews recent evidence,discusses the potential effects of GLP-1R agonists in CCA patients,and proposes underlying mechanisms that would benefit from further basic and clinical investigation. 展开更多
关键词 CARCINOGENESIS CHOLANGIOCARCINOMA Diabetes mellitus INCRETIN glucagon-like peptide 1 receptor
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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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Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer's disease?
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作者 李琳 《Neuroscience Bulletin》 SCIE CAS CSCD 2007年第1期58-65,共8页
Glucagon-like peptide- 1 (GLP- 1) has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus (T2DM). Both Alzheimer's disease (AD) and T2DM share some common pathophysiol... Glucagon-like peptide- 1 (GLP- 1) has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus (T2DM). Both Alzheimer's disease (AD) and T2DM share some common pathophysiologic hallmarks, such as amyloid β (Aβ), phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD. 展开更多
关键词 glucagon-like peptide 1 type 2 diabetes mellitus Alzheimer's disease
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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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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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Potential therapeutic targets for nonalcoholic fatty liver disease:Glucagon-like peptide 1 被引量:1
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作者 Yue-Hua Yin Li-Xuan Sang Bing Chang 《World Journal of Gastroenterology》 SCIE CAS 2023年第48期6235-6238,共4页
Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrat... Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrates(glucose,fructose,and fatty acids),leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury.The pathogenesis of this disease is largely associated with obesity,type 2 diabetes,and increasing age.To date,there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis.Since one of the pathogenic drivers of NASH is insulin resistance,therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH.Currently,the glucagon-like peptide-1 receptor agonist(GLP-1RA)semaglutide is a safe,well-studied therapeutic for NAFLD/NASH patients.Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis.However,improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD.Given the complex pathophysiology of NASH,combining therapies with complementary mechanisms may be beneficial.Researchers have conducted trials of semaglutide in combination with antifibrotic drugs.However,the results have not fully met expectations,and it cannot be ruled out that the reason is the short trial time.We should continue to pay increasing attention to GLP-1RAs. 展开更多
关键词 Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Antidiabetic drugs glucagon-like peptide 1 Semaglutide
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Effects of Glucagon-Like Peptide 1 on PDX-1, PAX-6 and NKx2.2 Gene Expressions in Isolated Pancreatic Islets 被引量:1
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作者 Dai Cui Wei Tang Cuiping Liu Kuanfeng Xu Chao Liu 《Journal of Nanjing Medical University》 2006年第3期141-144,共4页
Objective: To observe the effect of glucagon-like peptide 1 (GLP-1) on the gene expressions of transcription factors (PDX-1, PAX-6 and NKx2.2 ) in freshly isolated rat pancreatic islets and investigate the associ... Objective: To observe the effect of glucagon-like peptide 1 (GLP-1) on the gene expressions of transcription factors (PDX-1, PAX-6 and NKx2.2 ) in freshly isolated rat pancreatic islets and investigate the associated physiological and therapeutic implication of GLP-1. Methods: The isolated rat islets were incubated with 10 nmol/L GLP-1 for 1, 3 and 5 days, respectively. Total cellular RNA was extracted and the expressions of PDX-1, PAX-6 and NKx2.2 gene were detected by semiquantity RT-PCR. Results: Compared with the control group, the PDX-1, PAX-6 and NKx2.2 gene expressions were significantly increased after co-cultured with GLP-1 for 1 day (P 〈 0.05). The effect was shown in a time-dependent manner. All three gene expressions reached the peak on the 5th day. Conclusion: GLP-1 can improve the function of pancreatic islet by regulating the gene expressions of transcription factors in β cells. 展开更多
关键词 glucagon-like peptide 1 ISLET transcription factor diabetes mellitus
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Glucagon-like peptide 1 receptor governs Wnt signaling to promote bone formation
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《中国药理学通报》 CAS CSCD 北大核心 2015年第B11期7-7,共1页
Our previous investigation found that exendin-4 (Ex-4) , a peptide analogue of glucagon-like peptide 1 (GLP-1) , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did ... Our previous investigation found that exendin-4 (Ex-4) , a peptide analogue of glucagon-like peptide 1 (GLP-1) , induced bone formation probably by osteoblast activation. Nevertheless, previous investigations did not observe any expression of GLP-1 receptors in osteoblasts, indicating that the direct cell target of GLP-1 and its ana- logues might not be osteoblasts but some other types of cells yet to be identified. To elucidate the underlying mecha- nisms, we performed further investigation in the present study and found that GLP-1 receptor was only identified in bone marrow mesenchymal stem cells (BMSCs). Furthermore, activation of GLP-1 receptor by Ex-4 promoted the differentiation of B MSCs into osteoblast, which was associated with activation of PKA, nuclear translocation of [5- catenin, activation of PI3K/AKT and inhibition of GSK3β. Ex-4 also inhibited the adipocyte differentiation of BM- SCs, as evidenced by inhibition of PPARγ, lipoprotein lipase expression and lipid production. Blockade of GLP-1 receptor, PKA, PI3K or Wnt pathway, or respective knock-down of GLP-1 receptor and β-catenin in BMSCs inhib- ited the Ex-4 mediated effects. The results indicated that the GLP-1 receptor mediated osteoblastic differentiation and bone formation through stimulation of PKA/β-catenin signaling and inhibition of PKA/PI3IC/AKT/GSK3β? signaling pathway in BMSCs. The findings reveal a new role of GLP-1 receptor for regulating osteoblastic differentia- tion of B MSCs and may provide a molecular basis for novel anabolic therapeutics against osteoporosis. 展开更多
关键词 EXENDIN-4 glucagon-like peptide 1 RECEPTOR MESENCHYMAL stem cells OSTEOBLAST OSTEOPOROSIS
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Postprandial glucagon-like peptide 1 secretion is associated with urinary albumin excretion in newly diagnosed type 2 diabetes patients
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作者 Lu-Lu Song Na Wang +4 位作者 Jin-Ping Zhang Li-Ping Yu Xiao-Ping Chen Bo Zhang Wen-Ying Yang 《World Journal of Diabetes》 SCIE 2023年第3期279-289,共11页
BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate... BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1)and microalbuminuria in newly diagnosed T2DM patients.METHODS In total,760 patients were recruited for this cross-sectional study.The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were determined.RESULTS Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria(30 min GLP-1,16.7±13.3 pmol vs 19.9±15.6 pmol,P=0.007;120 min GLP-1,16.0±14.1 pmol vs 18.4±13.8 pmol,P=0.037).The corresponding area under the curve for active GLP-1(AUCGLP-1)was also lower in microalbuminuria patients(2257,1585 to 3506 vs 2896,1763 to 4726,pmol×min,P=0.003).Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR(r=0.159,r=0.132,r=0.206,respectively,P<0.001).The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%,which decreased with increasing quartiles of AUCGLP-1 levels(27.4%,25.3%,18.9%and 15.8%).After logistic regression analysis adjusted for sex,age,hemoglobin A1c,body mass index,systolic blood pressure,estimated glomerular filtration rate,homeostasis model assessment of insulin resistance,AUC_(glucose)and AUC_(glucagon)patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1(odds ratio=0.547,95%confidence interval:0.325-0.920,P=0.01).A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria.CONCLUSION Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients. 展开更多
关键词 MICROALBUMINURIA glucagon-like peptide 1 Type 2 diabetes NEPHROPATHY
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Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion 被引量:2
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作者 Benjamin S Maciejewski Tara B Manion Claire M Steppan 《World Journal of Gastrointestinal Pathophysiology》 CAS 2017年第4期161-175,共15页
AIM To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1(DGAT1) plays in postprandial gut peptide secretion and signaling.METHODS The standard experimental paradigm utilized to evaluate the incret... AIM To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1(DGAT1) plays in postprandial gut peptide secretion and signaling.METHODS The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge.Following a lipid challenge,plasma was collected via cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h.Incretin hormones [glucagon like peptide-1(GLP-1),peptide tyrosine-tyrosine(PYY) and glucose dependent insulinotropic polypeptide(GIP)] were then quantitated.The impact of pharmacological inhibition of DGAT1 on the incretin effect was evaluated in WT mice.Additionally,a comparison of loss of DGAT1 function either by genetic ablation or pharmacological inhibition.To further elucidate the pathways and mechanisms involved in the incretin response to DGAT1 inhibition,other interventions [inhibitors of dipeptidyl peptidase-IV(sitagliptin),pancreatic lipase(Orlistat),GPR119 knockout mice] were evaluated.RESULTS DGAT1 deficient mice and wildtype C57/BL6J mice werelipid challenged and levels of both active and total GLP-1 in the plasma were increased.This response was further augmented with DGAT1 inhibitor PF-04620110 treated wildtype mice.Furthermore,PF-04620110 was able to dose responsively increase GLP-1 and PYY,but blunt GIP at all doses of PF-04620110 during lipid challenge.Combination treatment of PF-04620110 and Sitagliptin in wildtype mice during a lipid challenge synergistically enhanced postprandial levels of active GLP-1.In contrast,in a combination study with Orlistat,the ability of PF-04620110 to elicit an enhanced incretin response was abrogated.To further explore this observation,GPR119 knockout mice were evaluated.In response to a lipid challenge,GPR119 knockout mice exhibited no increase in active or total GLP-1 and PYY.However,PF-04620110 was able to increase total GLP-1 and PYY in GPR119 knockout mice as compared to vehicle treated wildtype mice.CONCLUSION Collectively,these data provide some insight into the mechanism by which inhibition of DGAT1 enhances intestinal hormone release. 展开更多
关键词 glucagon-like peptide-1 peptide tyrosinetyrosine Glucose independent insulinotropic peptide ACYL-COA diacylglycerol acyltransferase-1 INCRETIN
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Antihypertensive Effect of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists
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作者 Marijana Tadic Cesare Cuspidi 《Cardiology Discovery》 2024年第1期38-42,共5页
An increasing body of evidence shows that new antidiabetic drugs—particularly sodium-glucose cotransporter 2(SGLT2)inhibitors and glucagon-like peptide 1(GLP-1)receptor agonists—have a beneficial effect on cardiovas... An increasing body of evidence shows that new antidiabetic drugs—particularly sodium-glucose cotransporter 2(SGLT2)inhibitors and glucagon-like peptide 1(GLP-1)receptor agonists—have a beneficial effect on cardiovascular outcome.The majority of these studies have been performed in patients with heart failure and the results have shown first positive effect on blood pressure(BP)reduction.These effects are more pronounced with SGLT2 inhibitors than with GLP-1 receptor agonists.However,the reasons and mechanisms of action inducing BP reduction are still not sufficiently clear.Proposed mechanisms of SGLT2 inhibitors involve the natriuretic effect,modification of the renin-angiotensin-aldosterone system,and/or the reduction in the sympathetic nervous system.GLP-1 receptor agonists have several mechanisms that are related to glycemic,weight,and BP control.Current data show that SGLT2 inhibitors have a stronger antihypertensive effect than GLP-1 receptor agonists,which is mainly related to their renal effect.Briefly,SGLT2 inhibitors increase the response to diuretics and decrease the meal-related antinatriuretic pressure by lowering post-prandial hyperglycemia and hyperinsulinemia and prevent proximal sodium reabsorption.SGLT2 inhibitors can be used as second-line therapy in patients with diabetes mellitus or heart disease and concomitant hypertension.This article aims to summarize current knowledge regarding the antihypertensive effect of SGLT2 inhibitors and GLP-1 receptor agonists. 展开更多
关键词 HYPERTENSION Sodium-glucose cotransporter 2 inhibitors glucagon-like peptide 1 receptor agonists Blood pressure
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Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury 被引量:6
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作者 Li-Xiong Chen Wei-Feng Zhang +1 位作者 Ming Wang Pi-Feng Jia 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第10期1782-1786,共5页
Calcitonin gene-related peptide(CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury(TBI) remains poorly understood. In t... Calcitonin gene-related peptide(CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury(TBI) remains poorly understood. In this study, 96 adult patients with TBI(enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group(36 males and 25 females, aged 38 ± 13 years) and severe TBI group(22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls(15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI. 展开更多
关键词 nerve regeneration calcitonin gene-related peptide severe traumatic brain injury prognosis biomarkers ENDOTHELIN-1 MORTALITY dynamic serum levels critical care medicine neural regeneration
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重组胰高血糖素样肽-1与人血清白蛋白融合蛋白的纯化及活性研究 被引量:3
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作者 陈家琪 高智慧 +2 位作者 朱元元 杨文博 白钢 《微生物学通报》 CAS CSCD 北大核心 2007年第5期871-874,共4页
利用构建的重组菌株Pichia pastoris GS115/GLP-1/HSA,在10L发酵罐中表达了胰高血糖素样肽-1与人血清白蛋白融合蛋白(GLP-1/HSA),表达量为63.6mg/L。发酵液经中空纤维柱浓缩、疏水层析、阴离子交换层析和凝胶过滤分离纯化,获得了较高纯... 利用构建的重组菌株Pichia pastoris GS115/GLP-1/HSA,在10L发酵罐中表达了胰高血糖素样肽-1与人血清白蛋白融合蛋白(GLP-1/HSA),表达量为63.6mg/L。发酵液经中空纤维柱浓缩、疏水层析、阴离子交换层析和凝胶过滤分离纯化,获得了较高纯度的GLP-1/HSA,经HPLC分析纯度达95.8%。进一步的体内活性分析结果表明,GLP-1/HSA不仅具有天然GLP-1的生物活性,而且在给药后4h仍能发挥显著性降血糖作用。以上结果表明,利用Pichia pastoris分泌型表达系统和建立的分离纯化方法,能获得大量较高纯度的GLP-1/HSA,为进一步研究和开发能够用于糖尿病临床治疗的长效GLP-1类似物奠定了基础。 展开更多
关键词 胰高血糖素样肽-1 人血清白蛋白 融合表达 纯化
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人胰高血糖素样肽-1与人血清白蛋白融合蛋白在毕赤酵母中的表达 被引量:2
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作者 龙娟 薛冲 +2 位作者 赵洪亮 杨晓红 刘志敏 《生物技术通讯》 CAS 2008年第4期488-492,共5页
目的:在巴斯德毕赤酵母中表达有降糖活性的人胰高血糖素样肽-1(hGLP-1)突变体(2Gly-hGLP-1)与人血清白蛋白(HSA)的融合蛋白。方法:为将GLP-1氨基酸序列第2位的丙氨酸(Ala)定点突变为甘氨酸(Gly),根据毕赤酵母偏爱密码子合成编码2Gly-hGL... 目的:在巴斯德毕赤酵母中表达有降糖活性的人胰高血糖素样肽-1(hGLP-1)突变体(2Gly-hGLP-1)与人血清白蛋白(HSA)的融合蛋白。方法:为将GLP-1氨基酸序列第2位的丙氨酸(Ala)定点突变为甘氨酸(Gly),根据毕赤酵母偏爱密码子合成编码2Gly-hGLP-1的基因;采用重叠PCR法拼接2Gly-hGLP-1和HSA的基因,使得2Gly-hGLP-1的C端与HSA的N端通过甘氨酸五肽接头连接;将该融合基因插入表达载体pPIC9构建为重组载体pPIC9/2Gly-hGLP-1-HSA,电击转化至毕赤酵母GS115细胞,通过表型筛选和诱导表达实验获得高效表达菌株;工程菌在5L发酵罐中培养后,对发酵产物进行分离纯化和生物学活性分析。结果:融合蛋白在5L发酵罐中的表达量约为200mg/L,经纯化后纯度可达95%以上;小鼠糖耐量实验表明该融合蛋白具有明显的控血糖活性。结论:在毕赤酵母中分泌表达的融合蛋白2Gly-hGLP-1-HSA具有降血糖活性。 展开更多
关键词 人胰高血糖素样肽 人血清白蛋白 融合蛋白 毕赤酵母
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多模态磁共振成像联合血清胰高血糖素样肽1检测诊断阿尔茨海默症的价值观察 被引量:2
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作者 郭翃江 窦立冬 +1 位作者 严之红 纪红 《中国CT和MRI杂志》 2020年第8期4-6,共3页
目的研究多模态磁共振联合血清胰岛高血糖素样肽1(GLP-1)检测诊断阿尔茨海默症(AD)的价值。方法将航天中心医院2018年06月~2019年06月间收治的30例AD患者纳为研究对象,并将30例认知功能正常的同龄老年患者纳为对照组,比较两组多模态MRI... 目的研究多模态磁共振联合血清胰岛高血糖素样肽1(GLP-1)检测诊断阿尔茨海默症(AD)的价值。方法将航天中心医院2018年06月~2019年06月间收治的30例AD患者纳为研究对象,并将30例认知功能正常的同龄老年患者纳为对照组,比较两组多模态MRI成像特点及血清GLP-1水平,分析MRI多模态成像联合血清GLP-1在诊断AD中的作用。结果多模态MRI提示,较对照组比,AD组患者存在广泛的灰质萎缩,双侧大脑半球大致对称的白质纤维束完整性受损,表现为FA值降低,MD值、RD值增加,穹隆体部及穹隆柱FA值下降,左侧内囊前后肢,左侧丘脑前辐射及双侧上额枕束的MD值或λ1值或RD值增加等;且AD组空腹状态下血清GLP-1水平显著高于对照组,服糖后1h、1.5h及2h后AD组血清GLP-1水平显著低于同时间段对照组水平(P<0.05)。结论多模型MRI能通过多参数有效提示AD患者脑组织形态及功能异常,此外,AD患者服糖前后血清GLP-1水平与健康者间存在显著差异,该改变在提示患者病情具有一定参考价值。 展开更多
关键词 多模态磁共振成像 血清胰高血糖素肽1 阿尔茨海默症
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生物素化微细纤维肽修饰IGF-1对急性心肌梗死兔血清炎性因子的影响 被引量:2
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作者 胡云华 肖祖克 《南昌大学学报(医学版)》 CAS 2018年第4期19-21,25,共4页
目的探讨生物素化微细纤维肽修饰胰岛素样生长因子-1(IGF-1)对急性心肌梗死(AMI)兔血清炎性因子的影响。方法将28只新西兰白兔随机分为对照组和实验1组、实验2组、实验3组,每组7只。对照组行假手术,实验1、2、3组建立AMI模型。建模成功... 目的探讨生物素化微细纤维肽修饰胰岛素样生长因子-1(IGF-1)对急性心肌梗死(AMI)兔血清炎性因子的影响。方法将28只新西兰白兔随机分为对照组和实验1组、实验2组、实验3组,每组7只。对照组行假手术,实验1、2、3组建立AMI模型。建模成功后,实验1组注射生物素化微细纤维肽修饰的IGF-1,实验2组注射未修饰的IGF-1,对照组和实验3组注射等剂量的生理盐水。干预1周后,采用酶联免疫吸附试验(ELISA)法检测血清白细胞介素-6(IL-6)、超敏C-反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)的水平。结果干预1周后,与对照组比较,实验1、2、3组血清IL-6、hs-CRP、TNF-α水平均显著升高(均P<0.05);与实验3组比较,实验1、2组血清IL-6、hs-CRP、TNF-α水平均显著降低(均P<0.05);与实验2组比较,实验1组血清IL-6、hs-CRP、TNF-α水平均显著降低(均P<0.05)。结论 IGF-1和生物素化微细纤维肽修饰的IGF-1均能够显著降低AMI兔炎性因子的水平,但生物素化微细纤维肽修饰的IGF-1效果更优。 展开更多
关键词 生物素化微细纤维肽修饰IGF-1 心肌梗死 急性 炎性因子 血清 动物 实验 白兔
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阿托伐他汀对心衰患者BNP和cTn1的影响作用 被引量:3
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作者 朱彩红 黄彩玲 关嘉良 《北方药学》 2016年第1期107-108,共2页
目的:探讨阿托伐他汀对心衰患者B型脑钠肽(BNP)和血清肌钙蛋白1(c Tn1)的变化影响。方法:选取我院2014年1~6月收治的80例心力衰竭患者,随机分为研究组和对照组,对照组给予常规抗心衰治疗,研究组在此基础上给予阿托伐他汀治疗,比... 目的:探讨阿托伐他汀对心衰患者B型脑钠肽(BNP)和血清肌钙蛋白1(c Tn1)的变化影响。方法:选取我院2014年1~6月收治的80例心力衰竭患者,随机分为研究组和对照组,对照组给予常规抗心衰治疗,研究组在此基础上给予阿托伐他汀治疗,比较两组BNP和c Tn1变化情况。结果:治疗前两组患者c Tn1和BNP水平对比差异无统计学意义(P〉0.05),经过治疗均明显下降,与治疗前比较差异有统计学意义(P〈0.05)。治疗后研究组c Tn1和BNP水平均较对照组低,差异有统计学意义(P〈0.05)。两组患者心血管死亡、卒中及非致死性心肌梗死发生率对比差异无统计学意义(P〉0.05)。心衰再住院发生率组间比较差异有统计学意义(P〈0.05)。结论:与常规抗心衰相比,阿托伐他汀可显著降低患者BNP和c Tn1水平,改善患者预后。 展开更多
关键词 心力衰竭 血清肌钙蛋白1 B型脑钠肽 阿托伐他汀
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GLP1R基因多态性与中国汉族人群2型糖尿病风险及血糖、血脂、胰岛功能的关系 被引量:2
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作者 郑文文 郑超 周心禾 《温州医科大学学报》 2021年第11期896-901,共6页
目的:探讨中国汉族人群胰高血糖素样肽1受体(GLP1R)基因rs3765467、rs2268657和rs6923761位点与2型糖尿病(T_(2)DM)的相关性及对血糖、血脂代谢和胰岛功能的影响。方法:采用竞争性等位基因特异性PCR检测GLP1R基因rs3765467、rs2268657和... 目的:探讨中国汉族人群胰高血糖素样肽1受体(GLP1R)基因rs3765467、rs2268657和rs6923761位点与2型糖尿病(T_(2)DM)的相关性及对血糖、血脂代谢和胰岛功能的影响。方法:采用竞争性等位基因特异性PCR检测GLP1R基因rs3765467、rs2268657和rs6923761位点的基因型,并结合血糖、血脂和胰岛功能进行分析。结果:T_(2)DM组GLP1R基因rs3765467位点CC基因型和C等位基因的频率均显著高于对照组(61.0%vs.51.9%,P=0.040;77.3%vs.72.3%,P=0.022)。在隐性模型中,T_(2)DM组rs3765467位点CC基因型频率显著高于对照组(61.0%vs.51.9%,P=0.011)。Logistic回归分析显示rs3765467位点CC基因型是T_(2)DM发病的独立危险因素(OR=1.724,95%CI=1.217~2.443,P=0.002)。rs3765467位点CC基因型HbA1c水平显著高于CT+TT基因型(t=-2.517,P=0.012);rs2268657位点GG基因型HDL-C水平显著高于GA+AA基因型(t=-2.162,P=0.031)。在T_(2)DM组中,rs3765467位点CC基因型FP-C、HOMA-β、HOMA-IR水平明显低于CT+TT基因型(均P<0.05)。结论:GLP1R基因rs3765467位点可能与中国汉族人群T_(2)DM的发病风险相关,GLP1R基因多态性可能影响血糖、血脂代谢及胰岛β细胞功能。 展开更多
关键词 胰高血糖素样肽1受体 基因多态性 2型糖尿病 血糖 血脂 胰岛功能
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