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GLP-1 diabetes

Kanwal Rehman, Mehwish Bagh Ali, Muhammad Sajid Hamid Akash
Glucagon-like peptide-1 (GLP-1) an incretin hormone, is known to regulate the glucose-mediated insulin secretion. However, reduction in the level of GLP-1 is considered to be a major cause for the reduction of GLP-1-dependent insulin secretory response. Genistein an isoflavone, is an important polyphenol and has wide range of therapeutic potentials, but its therapeutic effects alone and/or in combination with metformin on GLP-1 secretion have not been investigated yet. Hence, we aimed to investigate the stimulatory action of genistein in combination with metformin on GLP-1 via downregulation of inflammatory mediators, hyperlipidemia and hyperglycemia in alloxan-induced diabetic rats...
February 19, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ponnie Robertlee Dolo, Yong Shao, Chao Li, Xiaocheng Zhu, Libin Yao, Hui Wang
BACKGROUND: Gastric bypass with a proximal gastric pouch (Roux-en-Y gastric bypass) induces early diabetes remission. The effect of gastric bypass with a distal gastric pouch remains unknown. OBJECTIVE: To observe the effect on glucose tolerance and diabetes remission of gastric bypass with a distal gastric pouch. METHOD: A type 2 diabetes (T2D) model was created in 44 Sprague-Dawley (SD) rats that randomly underwent Roux-en-Y gastric bypass (RYGB, n = 8); gastric bypass with duodenal-jejunal transit (GB-DJT, n = 8); distal-pouch gastric bypass with duodenal-jejunal transit (DPGB-DJT, n = 8); distal-pouch gastric bypass with duodenal-jejunal bypass (DPGB-DJB, n = 8); sham (n = 6); and Roux-en-Y gastric bypass with esophageal re-anastomosis (RYGB-Er, n = 6) surgery...
February 18, 2019: Obesity Surgery
Yang Jing, Wang Zongming, Zhang Xilin
PURPOSE: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, is an antidiabetic drug. It has been shown to improve the Psoriasis Area and Severity Index (PASI) in patients with type 2 diabetes and psoriasis in clinical practice, but the mechanism remains somewhat unclear. We used lipopolysaccharides (LPS) to induce inflammatory response in keratinocytes and explore the mechanism. METHODS: The HaCat cells were incubated with LPS for 16 h and then were treated with liraglutide for 30 min...
February 15, 2019: Experimental and Molecular Pathology
John E Anderson, John L Leahy
No abstract text is available yet for this article.
February 15, 2019: American Journal of Medicine
Eisuke Kato
Plant materials have been widely studied for their preventive and therapeutic effects for type 2 diabetes mellitus (T2DM) and obesity. The effect of a plant material arises from its constituents, and the study of these bioactive compounds is important to achieve a deeper understanding of its effect at the molecular level. In particular, the study of the effects of such bioactive compounds on various biological processes, from digestion to cellular responses, is required to fully understand the overall effects of plant materials in these health contexts...
February 17, 2019: Bioscience, Biotechnology, and Biochemistry
Mei Zhou, Shuyi Chen, Peng Peng, Zhongya Gu, Jing Yu, Gang Zhao, Yanqiu Deng
Dulaglutide, a novel long-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is an incretin mimetic approved for type 2 diabetes mellitus (T2DM) treatment. Alzheimer's disease (AD) is called type 3 diabetes. The aim of this study is to explore the effects of dulaglutide on the learning and memory impairment in AD mice induced by injection of streptozocin (STZ) via intracerebroventricularly (i.c.v.). 32 male C57/BL6 mice were randomly divided into four groups: control group (CON); AD model group (STZ); dulaglutide treated (Dul); dulaglutide and exendin(9-39) (Ex)...
February 14, 2019: Biochemical and Biophysical Research Communications
Marzieh Salehi, Amalia Gastaldelli, David A D'Alessio
OBJECTIVE: Postprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that β-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB. DESIGN: Ten non-diabetic subjects with GB, and 9 body mass index (BMI)-matched and age-matched non-surgical controls (CN) with normal glucose tolerance had blood glucose clamped at ~7...
February 16, 2019: Gut
Min Ding, Qian-Hua Fang, Yuan-Tao Cui, Qi-Ling Shen, Qian Liu, Peng-Hua Wang, De-Min Yu, Chun-Jun Li
AIMS: High glucose (HG)-induced pancreatic β-cell apoptosis may be a major contributor to the progression of diabetes mellitus (DM). NADPH oxidase (NOX2) has been considered a crucial regulator in β-cell apoptosis. This study was designed to evaluate the impact of GLP-1 receptor agonist (GLP-1Ra) liraglutide on pancreatic β-cell apoptosis in diabetes and the underlying mechanisms involved. METHODS: The diabetic rat models induced by streptozotocin (STZ) and a high fat diet (HFD) received 12 weeks of liraglutide treatment...
January 2, 2019: Journal of Diabetes and its Complications
Irina Velikyan, Torsten Haack, Martin Bossart, Andreas Evers, Iina Laitinen, Philip Larsen, Oliver Plettenburg, Lars Johansson, Stefan Pierrou, Michael Wagner, Olof Eriksson
The glucagon receptor (GCGR) is emerging as an important target in anti-diabetic therapy, especially as part of the pharmacology of dual glucagon-like peptide-1/glucagon (GLP-1/GCG) receptor agonists. However, currently, there are no suitable biomarkers that reliably demonstrate GCG receptor target engagement. METHODS: Two potent GCG receptor peptide agonists, S01-GCG and S02-GCG, were labeled with positron emission tomography (PET) radionuclide gallium-68. The GCG receptor binding affinity and specificity of the resulting radiopharmaceuticals [68 Ga]Ga-DO3A-S01-GCG and [68 Ga]Ga-DO3A-S02-GCG were evaluated in HEK-293 cells overexpressing the human GCG receptor and on frozen hepatic sections from human, non-human primate, and rat...
February 15, 2019: EJNMMI Research
Yuetao Wen, Kunlun Wu, Yanfeng Xie, Wei Dan, Yan Zhan, Quanhong Shi
Glucagon-like peptide-1 (GLP-1) and its receptor, GLP-1R, are valuable tools in the therapy of type 2 diabetes mellitus. Although GLP-1R stimulation is also potentially applicable to neurological disorders, few investigators have evaluated its beneficial effects in neurological disease models. Thus, we aimed to look into the antiepileptic effects of GLP-1R on epilepsy and its underlying mechanisms. The cerebral cortex of 22 patients with temporal lobe epilepsy (TLE) and 16 patients with trauma were collected to the epilepsy and control groups, respectively...
February 12, 2019: Biochemical and Biophysical Research Communications
Grażyna Wójcicka, Mariusz Zaręba, Anna Warpas, Anna Jamroz-Wiśniewska, Marta Rusek, Grażyna Czechowska, Jerzy Bełtowski
Inflammation and oxidative stress are the two processes crucial in atherogenesis. Platelet-activating factor acetylhydrolase (PAF-AH), a plasma lipoprotein-associated enzyme, degrades pro-inflammatory lipids generated within oxidatively modified lipoproteins. Extensive evidence shows that incretin-based drugs, a new class of anti-diabetic agents, can provide cardiovascular protection that cannot be attributed to their glucose-lowering effects. The present study was undertaken to determine whether the antiatherogenic effects of the GLP-1(glucagon-like peptide-1) receptor agonist (exenatide) and DPP-4(dipeptidyl peptidase-4) inhibitors (sitagliptin) may occur via the regulation of platelet-activating factor acetylhydrolase (PAF-AH) activity/mass and inhibition of low-density lipoprotein (LDL) oxidation in the fructose-fed rats...
February 12, 2019: European Journal of Pharmacology
Luigi F Meneghini, Didac Mauricio, Emanuela Orsi, Nebojsa M Lalic, Anna M G Cali, Jukka Westerbacka, Peter Stella, Christophe Candelas, Valerie Pilorget, Riccardo Perfetti, Kamlesh Khunti
AIMS: To describe in a real-world setting the achievement of physician-selected individualized HbA1c targets in people with type 2 diabetes, newly or recently initiated on basal insulin, and the association of hypoglycemia with target achievement. MATERIALS AND METHODS: A 12-week, prospective, single-arm, observational study of adults with type 2 diabetes either newly initiated with any basal insulin or started on basal insulin within the preceding 12 months. At enrollment, eligible participants from 28 countries were treated with or without oral antihyperglycemic drugs and/or GLP-1 receptor agonists...
February 15, 2019: Diabetes, Obesity & Metabolism
Georgios A Christou, Niki Katsiki, John Blundell, Gema Fruhbeck, Dimitrios N Kiortsis
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3...
February 15, 2019: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Prakash Deedwania, Tushar Acharya
Diabetes mellitus is a major risk factor for cardiovascular (CV) disease. Conversely, CV disease is responsible for a majority of the deaths in patients with diabetes. Many drug trials have concentrated on blood glucose (hemoglobin A1c ) reduction. This strategy, while reducing microvascular outcomes like nephropathy and neuropathy, has little or no effect on reducing macrovascular events like heart attack, stroke, and heart failure. It has been postulated that hypoglycemia may counterbalance some of the beneficial effects of anti-hyperglycemic agents, but this is not proven...
February 15, 2019: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Xiang Zhang, Richard L Young, Michelle Bound, Sanyuan Hu, Karen L Jones, Michael Horowitz, Christopher K Rayner, Tongzhi Wu
OBJECTIVE: Cells releasing glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are distributed predominately in the proximal and distal gut, respectively. Hence, the region of gut exposed to nutrients may influence GIP and GLP-1 secretion and impact on the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). We evaluated glycemic and incretin responses to glucose administered into the proximal or distal small intestine and quantified the corresponding incretin effect and GIGD in health and type 2 diabetes mellitus (T2DM)...
February 14, 2019: Diabetes Care
Steven K Malin, Emily L Kullman, Amanda R Scelsi, Jean-Philippe Godin, Alastair B Ross, John P Kirwan
INTRODUCTION: Few data exist examining the effects of whole grain (WG) versus refined grain (RG) diets on glucose-stimulated insulin secretion (GSIS) and β-cell function. METHODS: In a double-blind crossover randomized controlled trial, 13 sedentary prediabetic adults (37.2±1.8 y, BMI: 33.6±1.4 kg/m2 , 2h glucose: 146.9±11.6 mg/dl) were provided isocaloric-matched WG and RG diets for 8-weeks each, with an 8-10 week washout between diets. Glucose, insulin and C-peptide metabolism was studied over 240 min following a 75g OGTT...
February 14, 2019: Molecular Nutrition & Food Research
Jeffrey I Mechanick, Alan J Garber, George Grunberger, Yehuda Handelsman, W Timothy Garvey
The American Association of Clinical Endocrinologists (AACE) has created a dysglycemia-based chronic disease (DBCD) multimorbidity care model consisting of four distinct stages along the insulin resistance-prediabetes-type 2 diabetes (T2D) spectrum that are actionable in a preventive care paradigm to reduce the potential impact of T2D, cardiometabolic risk, and cardiovascular events. The controversy of whether there is value, cost-effectiveness, or clinical benefit of diagnosing and/or managing the prediabetes state is resolved by regarding the problem, not in isolation, but as an intermediate stage in the continuum of a progressive chronic disease with opportunities for multiple concurrent prevention strategies...
November 2018: Endocrine Practice
Ahmed M Elmansi, Mohamed E Awad, Nada H Eisa, Dmitry Kondrikov, Khaled A Hussein, Alexandra Aguilar-Pérez, Samuel Herberg, Sudharsan Periyasamy-Thandavan, Sadanand Fulzele, Mark W Hamrick, Meghan E McGee-Lawrence, Carlos M Isales, Brian F Volkman, William D Hill
Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand...
February 10, 2019: Pharmacology & Therapeutics
Guillermo Umpierrez, Kevin M Pantalone, Charles M Atisso, Laura Fernández Landó, Hiren Patel
OBJECTIVE: There is limited information regarding the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on the relative contribution of basal hyperglycaemia (BHG) and post-prandial hyperglycaemia (PPHG) to overall hyperglycaemia across HbA1c categories. RESEARCH DESIGN AND METHODS: Data from five phase 3 studies (N=673) were pooled to assess the change in relative contributions of BHG and PPHG to overall hyperglycaemia across different HbA1c categories after 6 months of treatment intensification with dulaglutide 1...
February 12, 2019: Diabetes, Obesity & Metabolism
Pantelis Sarafidis, Charles J Ferro, Enrique Morales, Alberto Ortiz, Jolanta Malyszko, Radovan Hojs, Khaled Khazim, Robert Ekart, Jose Valdivielso, Denis Fouque, Gérard M London, Ziad Massy, Petro Ruggenenti, Esteban Porrini, Andrej Wiecek, Carmine Zoccali, Francesca Mallamaci, Mads Hornum
Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium-glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction...
February 1, 2019: Nephrology, Dialysis, Transplantation
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