Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes is a condition that is not completely treatable but life of a diabetic patient can be smoothed by preventing or delaying the associate conditions like diabetic retinopathy, nephropathy, impaired wound healing process, etc. Apart from conventional methods to regulate diabetic condition, new techniques using siRNA have been emerged to prevent the associated conditions. This paper focuses on how siRNA used as a tool to silence the expression of genes which plays critical role in pathogenesis of these conditions. A marked improvement in wound-healing process of diabetic patients has been observed with siRNA treatment by silencing of Keap1 gene. Glucagon plays critical role in glucose homoeostasis and increases blood glucose level during hypoglycaemia. Glucose homoeostasis is impaired in diabetic patient and suppressing the expression of glucagon secretion with siRNA is used to suppress the progress of diabetes. Similarly, silencing expression of several factors has demonstrated improvement of treatment of diabetic nephropathy, retinopathy and inflammation by the use of siRNA.
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PMID:siRNA: an alternative treatment for diabetes and associated conditions. 2975

Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial infarction, stroke, and peripheral vascular disease) and microvascular (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an effective strategy for preventing microvascular complications, but the extent to which it can reduce CV complications is less certain. Glucagon-like peptide-1 (GLP-1) agonists are potent glucose-lowering agents but also have potentially beneficial effects on other traditional (body weight, blood pressure (BP), and LDL cholesterol) and non-traditional risk factors (low grade inflammation and endothelial dysfunction). The results of four large CV outcome trials with GLP-1 agonists are now available. These have compared lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), and long-acting exenatide (EXSCEL) with placebo and standard of care over 2-4 years; four others (including with dulaglutide and albiglutide) are ongoing. LEADER and SUSTAIN-6 have demonstrated reductions in rates of major adverse CV events with active GLP-1 treatment but ELIXA and EXSCEL have not. In this review, we discuss the mechanisms by which GLP-1 receptor agonists act on the CV system and the design and conduct of these trials. Contrary to the assertions that (a) all GLP-1 agonists reduce CV disease in T2D but to different extents or (b) the magnitude of CV protection is predominantly related to glucose-lowering, we argue that CV benefit is specific to agents that provide longer acting agonism at the GLP-1 receptor. The mechanisms involve reduction in body weight and BP, and lowering of LDL-cholesterol and glucose, but pleiotropic effects-including suppression of low grade inflammation, vasodilation, and natriuresis-are also likely relevant.
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PMID:Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review. 3011 42

The prevalence of type 2 diabetes mellitus (T2DM), which is associated with cardiovascular morbidity and mortality, is increasing worldwide. Although there have been advances in diabetes treatments that reduce microvascular complications (nephropathy, neuropathy, retinopathy), many clinical studies have found that conventional oral hypoglycemic agents and glucose control alone failed to reduce cardiovascular disease. Thus, incretin-based therapies including glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) represent a new area of research, and may serve as novel therapeutics for treating hyperglycemia and modifying other cardiovascular risk factors. Recently, it has been confirmed that several drugs in these classes, including canagliflozin, empagliflozin, semaglutide, and liraglutide, are safe and possess cardioprotective effects. We review the most recent cardiovascular outcome trials on GLP-1RAs and SGLT-2Is, and discuss their implications for treating patients with T2DM in terms of protective effects against cardiovascular disease.
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PMID:The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes. 3109

There has been an increase in the range of non-insulin anti-hyperglycaemic agents used to treat type 2 diabetes. With the globally rising rates of type 2 diabetes and complications such as diabetic retinopathy, it is important for ophthalmologists to be aware of these new agents and their impacts on diabetic retinopathy and diabetic macular oedema. We conducted a review of the literature to determine if there were any beneficial or harmful effects of the currently used anti-hyperglycaemic agents on diabetic retinopathy or diabetic macular oedema. Our review of the current literature found that apart from thiazolidinediones, anti-hyperglycaemic agents have been reported to have beneficial or neutral effects on diabetic eye complications. Thiazolidinediones (pioglitazone is the only one currently available) have been linked to incident or worsening diabetic macular oedema, although the rate is believed to be low. Glucagon-like peptide 1 (GLP1) agonists (incretins) in general are beneficial except semaglutide which is associated with increased rates of diabetic retinopathy complications. These results have implications for selection of anti-hyperglycaemic agents for patients with diabetic retinopathy or macular oedema. Further studies need to be conducted to identify if reported beneficial effects are independent of the impact of glycaemic control. Early worsening of retinopathy with tight glycaemic control should also be noted in interpretation of future studies.
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PMID:New anti-hyperglycaemic agents for type 2 diabetes and their effects on diabetic retinopathy. 3122 89

Incretin contains two peptides named glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Drug therapy using incretin has become a new strategy for diabetic treatments due to its significant effects on improving insulin receptors and promoting insulinotropic secretion. Considering the fact that diabetes millitus is a key risk factor for almost all age-related diseases, the extensive protective roles of incretin in chronic diseases have received great attention. Based on the evidence from animal experiments, where incretin can protect against the pathophysiological processes of neurodegenerative diseases, clinical trials for the treatments of Alzheimer's disease (AD) and Parkinson's disease (PD) patients are currently ongoing. Moreover, the protective effect of incretin on heart has been observed in cardiac myocytes, smooth muscle cells and endothelial cells of vessels. Meanwhile, incretin can also inhibit the proliferation of aortic vascular smooth muscle cells, which can induce atherosclerogenesis. Incretin is also beneficial for diabetic microvascular complications, including nephropathy, retinopathy and gastric ulcer, as well as the hepatic-related diseases such as NAFLD and NASH. Besides, the anti-tumor properties of incretin have been proven in diverse cancers including ovarian cancer, pancreas cancer, prostate cancer and breast cancer.
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PMID:Protective Effects of Incretin Against Age-Related Diseases. 3162 2

Glucagon-like receptor agonists (GLP-1RAs) are included in current national and international guidelines as second-line treatment especially in patients with type 2 diabetes and concomitant cardiovascular disease (CVD). First-generation GLP-1RAs were two- or once-daily injectables, but longer-acting GLP-1RAs have now been developed for once-weekly administration - e.g., exenatide ER, dulaglutide and semaglutide. With semaglutide, the same prolongation principle as designed in liraglutide is used (spacer and fatty acid chain). However, the similarity to endogenous human GLP-1 is well preserved, sharing 94% homology. It is administered with a simple device and without resuspension before use. The efficacy and safety of semaglutide have been investigated in an extensive clinical development program including more than 9,000 patients with type 2 diabetes. Semaglutide has been compared head-to-head with a dipeptidyl peptidase-4 (DPP4)-inhibitor, GLP-1RAs and basal insulin. Further head-to-head studies are awaiting that compare semaglutide against a sodium-dependent-glucose transporter-2 (SGLT2)-inhibitor. In these studies, semaglutide was found to provide significant and clinically relevant reductions in HbA1c, fasting plasma glucose (FPG), glucose excursions, body weight and blood pressure. The reduction in glycaemic parameters was more pronounced than that in the comparator GLP-1RAs. The rate of hypoglycemia is very low during treatment with semaglutide if not combined with sulphonylureas or insulin. A cardiovascular outcome trial (CVOT) was performed before the approval of semaglutide, at the request of legal authorities. Not only non-inferiority was confirmed, but also superiority compared with placebo used in a population of patients with type 2 diabetes and CVD treated with oral antihyperglycaemic drugs (OADs) and/or insulin with regard to the primary composite endpoint: death from cardiovascular (CV) causes, nonfatal myocardial infarction or nonfatal stroke. The safety of treatment with semaglutide in patients with type 2 diabetes has been extensively investigated. Overall, gastrointestinal side effects dominate, as observed with other GLP-1RAs, and was observed in the same range as for comparator GLP-1RAs. As observed with other GLP-1RAs, side effects such as nausea and vomiting diminished over time during continuous treatment. Regarding microvascular complications, an unexpected increase in diabetes-related retinopathy was observed in the CVOT; Semaglutide Unabated Sustainability in Treatment of Type 2 diabetes' [SUSTAIN 6]), but not in other studies. The reason for this increase is not finally elucidated, but may be due to a nonspecific effect of a rapid decrease in glycaemic parameters in patients with preexisting retinopathy with high HbA1c at the start of the treatment. There is currently a warning in the Summary of Product Characteristics (SmPC) for semaglutide concerning treatment in patients with preexisting retinopathy. Further studies are needed to clarify this.
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PMID:Clinical potential of treatment with semaglutide in type 2 diabetes patients. 3184 22


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