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Search results for: Glucagon like peptide 1 receptor

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#33660198   2021/03/04 To Up

Oral Semaglutide Reduces HbA and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.

The efficacy and safety of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, were investigated in patients with type 2 diabetes (T2D) in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) programme. The current post-hoc exploratory subgroup analyses evaluated outcomes by background medication and insulin regimen subgroups.
Richard E Pratley, Matthew J Crowley, Mette Gislum, Christin L Hertz, Thomas B Jensen, Kamlesh Khunti, Ofri Mosenzon, John B Buse

1231 related Products with: Oral Semaglutide Reduces HbA and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.

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#33658023   2021/03/03 To Up

GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo.

Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). However, whether GRK2 affects insulin secretion or if GRK2 can control incretin actions in vivo remains to be analyzed.
Alba C Arcones, Rocío Vila-Bedmar, Mercedes Mirasierra, Marta Cruces-Sande, Mario Vallejo, Ben Jones, Alejandra Tomas, Federico Mayor, Cristina Murga

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#33655453   2021/03/02 To Up

Glucose-Lowering Medications and Cardiovascular Outcomes.

The purpose of this review is to examine recent evidence supporting CV safety profile and improvement of CV outcomes of some of the newer classes of diabetic medications.
Madhan Shanmugasundaram, J R Exequiel Pineda, Sangeetha Murugapandian

2936 related Products with: Glucose-Lowering Medications and Cardiovascular Outcomes.

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#33652942   2021/02/26 To Up

Treatments for NAFLD: State of Art.

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic liver disease in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults in the general population and up to 70% of patients with type 2 diabetes (T2DM). Despite the current knowledge of the epidemiology, pathogenesis, and natural history of NAFLD, no specific pharmacological therapies are until now approved for this disease and, consequently, general strategies have been proposed to manage it. They include: (a) lifestyle change in order to promote weight loss by diet and physical activity, (b) control of the main cardiometabolic risk factors, (c) correction of all modifiable risk factors leading the development and progression of advanced forms of NAFLD, and (d) prevention of hepatic and extra-hepatic complications. In the last decade, several potential agents have been widely investigated for the treatment of NAFLD and its advanced forms-shedding some light but casting a few shadows. They include some glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants (such as vitamin E), statins or other lipid lowering agents, bile and non-bile acid farnesoid X activated receptor (FXR) agonists, and others. This narrative review discusses in detail the different available approaches with the potential to prevent and treat NAFLD and its advanced forms.
Alessandro Mantovani, Andrea Dalbeni

1724 related Products with: Treatments for NAFLD: State of Art.

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#33651460   2021/03/02 To Up

Titratable Fixed-Ratio Combination of Basal Insulin Plus a GLP-1 Receptor Agonist: A Novel, Simplified Alternative to Premix Insulin for Type 2 Diabetes.

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycemic improvements to basal insulin but at the expense of increased hypoglycemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA reductions, lower risk of hypoglycemia, and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and FRCs of basal insulin plus GLP-1 RAs is currently in progress, which should help clarify outcomes for each treatment option. The current article discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option. This article is protected by copyright. All rights reserved.
Fernando Gomez-Peralta, Ebaa Al-Ozairi, Edward B Jude, Xiaoying Li, Julio Rosenstock

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#33645250   2021/03/01 To Up

Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms.

The aim of this study was to explore individual amino acid-stimulated GLP-1 responses and the underlying stimulatory mechanisms, as well as to identify the amino acid-sensing-receptors involved in amino acid-stimulated GLP-1 release. Experiments were primarily based on isolated perfused rat small intestines, which have intact epithelial polarization allowing discrimination between luminal and basolateral mechanisms as well as quantitative studies of intestinal absorption and hormone secretion. Expression analysis of amino acid sensors on isolated murine GLP-1 secreting L-cells was assessed by qPCR. We found that L-valine powerfully stimulated GLP-1 secretion but only from the luminal side (2.9-fold increase). When administered from the vascular side, L-arginine and the aromatic amino acids stimulated GLP-1 secretion equally (2.6-2.9 fold increases). Expression analysis revealed that Casr expression was enriched in murine GLP-1 secreting L-cells, whereas Gpr35, Gprc6a, Gpr142, Gpr93 (Lpar5) and the umami taste receptor subunits Tas1r3 and Tas1r1 were not. Consistently, activation of GPR35, GPR93, GPR142 and the umami taste receptor with specific agonists or allosteric modulators did not increase GLP-1 secretion (P>0.05 for all experiments), whereas vascular inhibition of CaSR reduced GLP-1 secretion in response to luminal infusion of mixed amino acids. In conclusion, amino acids differ in their capacity to stimulate GLP-1 secretion. Some amino acids stimulated secretion only from the intestinal lumen, while other amino acids exclusively stimulated secretion from the vascular side, indicating that amino acid-stimulated GLP-1 secretion involves both apical and basolateral (post-absorptive) sensing mechanisms. Sensing of absorbed amino acids involves CaSR activation as vascular inhibition of CaSR markedly diminished amino acid stimulated GLP-1 release.
Ida Marie Modvig, Rune Ehrenreich Kuhre, Sara L Jepsen, Stella Xu, Maja S Engelstoft, Kristoffer Lihme Egerod, Thue W Schwartz, Cathrine Ørskov, Mette M Rosenkilde, Jens J Holst

2613 related Products with: Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms.

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#33641073   2021/02/27 To Up

Exendin-4, a glucagon-like peptide receptor agonist, facilitates osteoblast differentiation via connexin43.

To investigate whether exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, affects connexin 43 (Cx43) expression in osteoblasts, and determine the specific mechanism underlying Cx43 modulation by Ex-4.
Jin Hong Chen, Chen Shen, Haram Oh, Ji Hyun Park

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#33640604   2021/02/25 To Up

Liraglutide regulates lipid metabolism via FGF21- LKB1- AMPK- ACC1 pathway in white adipose tissues and macrophage of type 2 diabetic mice.

Liraglutide (LRG), a glucagon-like peptide 1 analogue (GLP1A), could decrease body mass of type 2 diabetes (T2DM), but the exact molecular mechanism of LRG has not been elucidated. This study was performed to explore whether LRG regulated TG synthesis via secretion of FGF21 and modulating AMP-dependent protein kinase (AMPK) pathway in an autocrine mode. Two-month-old male C57BL/6 mice were fed high-fat diet (HFD) for 4 months followed by injection of 30 mg/kg streptozotocin (STZ) to induce state of T2DM. Then DM mice were given LRG (0.4 mg/kg/d) for 4 months. Body mass, serum lipids and FGF21 levels, related gene expression were analyzed. Lipopolysaccharide (LPS)-induced RAW264.7 cells were treated with palmitic acid and different concentrations of LRG. Then Exendin (9-39), siRNA targeted to liver kinase B1 (LKB1) and Compound C were used to confirm the signaling pathway. LRG decreased adipocyte size, increased secretion of FGF21, and promoted phosphorylation of LKB1, AMPK and Acetyl coenzyme A carboxylase 1 (ACC1) in white adipose tissue (WAT) of DM mice. LRG also increased phosphorylation of fibroblast growth factor receptor 3 (FGFR3), LKB1, AMPK and ACC1 via FGF21 secretion, which ultimately inhibited synthesis of TG in macrophage. In conclusion, FGF21 is induced to be expressed in macrophage by LRG, which then activates LKB1-AMPK-ACC1 pathway in an autocrine manner.
Nan Zhang, Chao Liu, Yi Zhang, Dongmei Xu, Li Gui, Yunxia Lu, Qiu Zhang

1574 related Products with: Liraglutide regulates lipid metabolism via FGF21- LKB1- AMPK- ACC1 pathway in white adipose tissues and macrophage of type 2 diabetic mice.

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#33636739   2021/02/26 To Up

Double Diabetes: A Growing Problem Requiring Solutions.

The growing proportion of type 1 diabetes mellitus (T1DM) patients with clinical features of insulin resistance (IR) has led to the description of a distinctive T1DM subgroup, still unrecognised by current guidelines, called double diabetes, assumingly associated with poorer metabolic phenotype and increased risk of micro- and macrovascular complications. The main goal of identifying double diabetes, estimated to be present in up to half of T1DM patients, is timely implementation of appropriate therapeutic interventions to reduce the increased risk of chronic complications and other adverse metabolic traits associated with this condition. Proposed diagnostic criteria are largely divided into three different groups: family history of type 2 diabetes mellitus (T2DM), obesity/metabolic syndrome, and IR. Estimated glucose disposal rate may prove the most reliable marker of double diabetes. In addition to general measures (diet, physical activity, antihypertensive, and lipid-lowering medications, etc.) and development of new insulin preparations with more hepatic action, double diabetes patients may derive more benefit from agents developed for T2DM. Indeed, such potentially promising agents include glucagon-like peptide-1 receptor agonists, sodium-glucose contrasporter-2 inhibitors, and their combination. We are now awaiting long-term trials assessing metabolic and vascular benefits of these medications in double diabetes.
Djordje S Popovic, Nikolaos Papanas

2853 related Products with: Double Diabetes: A Growing Problem Requiring Solutions.

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