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https://www.readbyqxmd.com/read/28822958/therapeutic-molecules-against-type-2-diabetes-what-we-have-and-what-are-we-expecting
#1
REVIEW
Ashwini Kumar, Sudhanshu Kumar Bharti, Awanish Kumar
World Health Organization (WHO) has identified diabetes as one of the fastest growing non-communicable diseases with 422 million patients around the world in 2014. Diabetes, a metabolic disease, is characterized primarily by hyperglycemia which results in various macrovascular and microvascular complications like cardiovascular disease and neuropathies which can significantly deteriorate the quality of life. The body either does not manufactures enough insulin (type 1 diabetes or T1DM) or becomes insensitive to physiologically secreted insulin or both (type 2 diabetes or T2DM)...
April 9, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28822847/intestinal-adaptations-following-bariatric-surgery-towards-the-identification-of-new-pharmacological-targets-for-obesity-related-metabolic-diseases
#2
REVIEW
Lara Ribeiro-Parenti, Jean-Baptiste Cavin, Maude Le Gall
Although the gastrointestinal tract is the primary target of bariatric surgery, its contributions to the metabolic changes observed after surgery are still underestimated. Changes in the number of incretin-producing cells could result in the modified hormonal response seen after surgery. Additionally, the rate of absorption and consumption of glucose could contribute to the ameliorated glycaemia. Moreover, decreased intestinal permeability could prevent endotoxemia. Recently, numerous studies have focused on intestinal adaptation following bariatric surgeries...
August 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28822777/managing-the-course-of-diabetic-kidney-disease-from-the-old-to-the-new
#3
REVIEW
Ronald M Goldenberg, Murray Berall, Christopher T M Chan, David Z I Cherney, Julie A Lovshin, Philip A McFarlane, Peter A Senior, Subodh Verma, Jordan J Weinstein
Diabetic kidney disease (DKD) is a group of chronic kidney diseases that is associated with significant cardiovascular as well as all-cause morbidity and mortality. Although DKD is often progressive in nature, its evolution can be modified by intensive management of glycemia and blood pressure and inhibition of the renin-angiotensin-aldosterone system. This review provides an overview of how multifactorial interventions can provide renal protection and includes a discussion of the nonglycemic effects of incretin-based diabetes therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors) and sodium-glucose cotransporter-2 inhibitors within the kidney in patients with type 2 diabetes...
August 16, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#4
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#5
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28803984/canagliflozin-potentiates-glp-1-secretion-and-lowers-the-peak-of-gip-secretion-in-rats-fed-a-high-fat-high-sucrose-diet
#6
Tohru Hira, Toshiki Koga, Kazuyo Sasaki, Hiroshi Hara
The glucose-induced secretion of incretins, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), is dependent on luminal glucose levels and transport of glucose via the sodium-glucose transporter 1 (SGLT1) in the small intestine. Because GLP-1 and GIP function in decreasing and increasing the body weight, respectively, we aimed to analyze the effect of transient inhibition of SGLT1 by canagliflozin on incretin secretion in an obese rat model. Male Sprague-Dawley rats were maintained on a high-fat high-sucrose diet for 6-7 weeks, and plasma GLP-1 and GIP levels were measured using an oral glucose tolerance test (OGTT)...
August 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28800948/comparative-effects-of-intraduodenal-fat-and-glucose-on-the-gut-incretin-axis-in-healthy-males
#7
Tongzhi Wu, Christopher K Rayner, Linda E Watson, Karen L Jones, Michael Horowitz, Tanya J Little
BACKGROUND: The interaction of nutrients with the small intestine stimulates the secretion of numerous enteroendocrine hormones that regulate postprandial metabolism. However, differences in gastrointestinal hormonal responses between the macronutrients are incompletely understood. In the present study, we compared blood glucose and plasma hormone concentrations in response to standardised intraduodenal (ID) fat and glucose infusions in healthy humans. METHODS: In a parallel study design, 16 healthy males who received an intraduodenal fat infusion were compared with 12 healthy males who received intraduodenal glucose, both at a rate of 2kcal/min over 120min...
August 8, 2017: Peptides
https://www.readbyqxmd.com/read/28799803/nutrition-inflammation-and-liver-spleen-axis
#8
Luigi Barrea, Carolina Di Somma, Giovanna Muscogiuri, Giovanni Tarantino, Gian Carlo Tenore, Francesco Orio, Annamaria Colao, Silvia Savastano
Chronic low-grade systemic inflammation represents a mechanism common to many diseases linked to atherosclerosis-related pathways. There is a growing body of evidence indicating that the combination of food quantity and quality along with genetic susceptibility are able to induce the aberrant activation of innate immune signalling, which initially contributes to chronic low-grade inflammation. Liver represents the central player to inflammatory response. Dietary/metabolic factors contribute to the pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD), the main causes of liver disease in the Western world...
August 11, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28799326/glp-1-conjugated-to-rhsa-variants-with-modified-fcrn-binding-properties-impact-on-molecular-structure-and-half-life
#9
Jens Thostrup Bukrinski, Pernille Sønderby, Filipa Antunes, Birgitte Andersen, Esben Gjerloeff Wedebye Schmidt, Guenther H H J Peters, Pernille Harris
Glucagon-like peptide 1 (GLP-1) is a small incretin hormone stimulated by food intake, resulting in an amplification of the insulin response. Though interesting as a drug candidate for the treatment of type 2 diabetes mellitus, its short plasma half-life of less than 3 minutes limits its clinical use. A strategy to extend the half-life of GLP-1 utilizes the long half-life of human serum albumin (HSA) by combining the two via chemical conjugation or genetic fusion. HSA has a plasma half-life of around 21 days owing to its interaction with the neonatal Fc receptor (FcRn) expressed in endothelial cells of blood vessels, which rescues circulating HSA from lysosomal degradation...
August 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/28797248/the-role-of-bariatric-surgery-to-treat-diabetes-current-challenges-and-perspectives
#10
REVIEW
Chrysi Koliaki, Stavros Liatis, Carel W le Roux, Alexander Kokkinos
Bariatric surgery is emerging as a powerful weapon against severe obesity and type 2 diabetes mellitus (T2DM). Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to treat T2DM, especially in light of accumulating evidence that surgery with gastrointestinal manipulations may result in T2DM remission (metabolic surgery). The major mechanisms mediating the weight loss-independent effects of bariatric surgery comprise effects on tissue-specific insulin sensitivity, β-cell function and incretin responses, changes in bile acid composition and flow, modifications of gut microbiota, intestinal glucose metabolism and increased brown adipose tissue metabolic activity...
August 10, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#11
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28793331/characterization-of-the-post-prandial-insulinemic-response-and-low-glycaemic-index-of-a-soy-beverage
#12
Jose Ce Serrano, Meritxell Martín-Gari, Anna Cassanye, Ana Belen Granado-Serrano, Manuel Portero-Otín
Soybean is recognized as rich source of bioactive compounds for the improvement of glucose homeostasis. However, the post-prandial mechanisms of action have not been extensively described. The aim of this study is to determine the changes in glucose homeostasis and related factors after acute intake of a soy beverage. Twenty-nine subjects (15 women and 14 men, with an average age of 19.5 ± 1.2) ingested 500 mL of water, glucose (20.5 g/500 mL) and soy beverage (20 g of carbohydrate) in three separate sessions...
2017: PloS One
https://www.readbyqxmd.com/read/28780756/potential-hormone-mechanisms-of-bariatric-surgery
#13
REVIEW
Georgios K Dimitriadis, Manpal S Randeva, Alexander D Miras
PURPOSE OF REVIEW: In recent years, the role of the gastrointestinal (GI) tract in energy homeostasis through modulation of the digestion and absorption of carbohydrates and the production of incretin hormones is well recognized. RECENT FINDINGS: Bariatric surgery for obesity has been a very effective method in substantially improving weight, and numerous studies have focused on intestinal adaptation after bariatric procedures. A number of structural and functional changes in the GI tract have been reported postsurgery, which could be responsible for the altered hormonal responses...
August 5, 2017: Current Obesity Reports
https://www.readbyqxmd.com/read/28778048/risk-stratification-of-patients-with-diabetes-and-the-role-of-sodium-glucose-co-transporter-inhibitors-2-during-ramadan-fasting
#14
Zaina Adnan
The month of Ramadan represents a golden opportunity for better management of patients with diabetes not only during Ramadan month, but also through the entire year. Pre Ramadan period is crucial for evaluating and preparing patients with diabetes intending to Fast Ramadan. The risk stratification categories should take into consideration patients with diabetes having specific conditions such as nephrotic syndrome who are predisposed to thrombosis independent to their estimated glomerular filtration rate and glycated haemoglobin...
July 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28777946/engineered-epidermal-progenitor-cells-can-correct-diet-induced-obesity-and-diabetes
#15
Jiping Yue, Xuewen Gou, Yuanyuan Li, Barton Wicksteed, Xiaoyang Wu
Somatic gene therapy is a promising approach for treating otherwise terminal or debilitating diseases. The human skin is a promising conduit for genetic engineering, as it is the largest and most accessible organ, epidermal autografts and tissue-engineered skin equivalents have been successfully deployed in clinical applications, and skin epidermal stem/progenitor cells for generating such grafts are easy to obtain and expand in vitro. Here, we develop skin grafts from mouse and human epidermal progenitors that were engineered by CRISPR-mediated genome editing to controllably release GLP-1 (glucagon-like peptide 1), a critical incretin that regulates blood glucose homeostasis...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777938/engineering-skin-with-skinny-genes
#16
Anika Böttcher, Heiko Lickert, Matthias Tschöp
The increasing prevalence of obesity and diabetes is an urgent worldwide health challenge. Now in Cell Stem Cell, Yue et al. (2017) report a proof-of-concept study using genetically engineered skin transplants that produce the incretin GLP-1 to prevent diet-induced obesity, suggesting a powerful approach for treating metabolic disorders.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28776152/glucose-metabolism-parameters-and-post-prandial-glp-1-and-glp-2-release-largely-vary-in-several-distinct-situations-a-controlled-comparison-among-individuals-with-crohn-s-disease-and-individuals-with-obesity-before-and-after-bariatric-surgery
#17
Daniéla Oliveira Magro, Everton Cazzo, Paulo Gustavo Kotze, Ana Carolina Junqueira Vasques, Carlos Augusto Real Martinez, Elinton Adami Chaim, Bruno Geloneze, José Carlos Pareja, Cláudio Saddy Rodrigues Coy
BACKGROUND: This study aims to compare the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 among individuals with Crohn's disease (CD), obese individuals before and after bariatric surgery, and healthy controls. METHODS: This an exploratory cross-sectional study that involved five groups of patients (two groups of individuals with CD-active and inactive), bariatric patients (pre- and post-surgery, who were their own controls), and a distinct separated control group of healthy volunteers...
August 3, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28769799/allspice-and-clove-as-source-of-triterpene-acids-activating-the-g-protein-coupled-bile-acid-receptor-tgr5
#18
Angela Ladurner, Martin Zehl, Ulrike Grienke, Christoph Hofstadler, Nadina Faur, Fátima C Pereira, David Berry, Verena M Dirsch, Judith M Rollinger
Worldwide, metabolic diseases such as obesity and type 2 diabetes have reached epidemic proportions. A major regulator of metabolic processes that gained interest in recent years is the bile acid receptor TGR5 (Takeda G protein-coupled receptor 5). This G protein-coupled membrane receptor can be found predominantly in the intestine, where it is mainly responsible for the secretion of the incretins glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). The aim of this study was (i) to identify plant extracts with TGR5-activating potential, (ii) to narrow down their activity to the responsible constituents, and (iii) to assess whether the intestinal microbiota produces transformed metabolites with a different activity profile...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28768173/the-sustained-effects-of-a-dual-gip-glp-1-receptor-agonist-nnc0090-2746-in-patients-with-type-2-diabetes
#19
Juan Pablo Frias, Edward J Bastyr, Louis Vignati, Matthias H Tschöp, Christophe Schmitt, Klara Owen, Rune Haubo Christensen, Richard D DiMarchi
Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28767692/insulin-receptor-signaling-and-glucagon-like-peptide-1-effects-on-pancreatic-beta-cells
#20
Nunzia Caporarello, Cristina Parrino, Vincenzo Trischitta, Lucia Frittitta
Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i...
2017: PloS One
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