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https://www.readbyqxmd.com/read/29674332/potent-sglt1-2-dual-inhibition-improves-glycemic-control-without-marked-gastrointestinal-adaptation-or-colonic-microbiota-changes-in-rodents
#1
Fuyong Du, Simon Hinke, Cassandre Cavanaugh, David Polidori, Nathanial Wallace, Thomas Kirchner, Matthew Jennis, Wensheng Lang, Gee-Hong Kuo, Micheal Gaul, James Lenhard, Keith Demarest, Nadim J Ajami, Yin Liang, Pamela J Hornby
The sodium/glucose cotransporters (SGLT1 and SGLT2) transport glucose across the intestinal brush border and kidney tubule. Dual SGLT1/2 inhibition could reduce hyperglycemia more than SGLT2-selective in patients with Type 2 Diabetes; however, questions remain about altered gastrointestinal (GI) luminal glucose and tolerability. Therefore, this was evaluated in slc5a1-/- mice or using a potent dual inhibitor (cmpd 8; SGLT1 Ki = 1.5±0.5nM 100 fold > potency than phlorizin; SGLT2 Ki = 0.4±0.2 nM). 13C6-glucose uptake was quantified in slc5a1 -/- mice and in isolated rat jejunum...
April 19, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29547706/clinical-implications-of-current-cardiovascular-outcome-trials-with-sodium-glucose-cotransporter-2-sglt2-inhibitors
#2
REVIEW
Soo Lim, Robert H Eckel, Kwang Kon Koh
The final goal in the management of patients with type 2 diabetes (T2D) is reduction in cardiovascular (CV) complications and total mortality. Various factors including hyperglycemia contribute to these complications and mortality directly and indirectly. In recent years, large-scale CV outcome trials with new antidiabetic medications, such as dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and sodium glucose cotransporter-2 (SGLT2) inhibitors, have been completed...
March 8, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29531541/sitagliptin-accelerates-endothelial-regeneration-after-vascular-injury-independent-from-glp1-receptor-signaling
#3
Friederike Remm, Nicolle Kränkel, Daniela Lener, Daniel J Drucker, Sieghart Sopper, Christoph Brenner
Introduction: DPP4 inhibitors (gliptins) are commonly used antidiabetic drugs for the treatment of type 2 diabetes. Gliptins also act in a glucose-independent manner and show vasoregenerative effects. We have shown that gliptins can remarkably accelerate vascular healing after vascular injury. However, the underlying mechanisms remain unclear. Here, we examined potential signaling pathways linking gliptins to enhanced endothelial regeneration. Methods and Results: We used wild-type and GLP1 receptor knockout ( Glp1r -/- ) mice to investigate the underlying mechanisms of gliptin-induced reendothelialization...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29509291/short-bowel-syndrome-influence-of-nutritional-therapy-and-incretin-glp1-on-bone-marrow-adipose-tissue
#4
Luciana T Parreiras-E-Silva, Iana M de Araújo, Jorge Elias, Marcello H Nogueira-Barbosa, Vivian M M Suen, Julio S Marchini, Jéssica Bonella, Andressa K Nahas, Carlos E G Salmon, Francisco J A de Paula
Energy deprivation leads to a decrease in white adipose tissue and bone mineral density (BMD), while simultaneously inducing the expansion of marrow adipose tissue (MAT). In short bowel syndrome (SBS), parenteral nutrition mitigates the deterioration of nutritional status, including decreases in MAT. Osteoporosis is, however, a frequent complication of SBS. The objective of our study here was to evaluate the association of fat deposit sites (subcutaneous and visceral adipose tissues: intrahepatic lipid (IHL) and MAT) and the incretin glucagon-like peptide 1 (GLP1) with BMD in individuals with SBS...
March 6, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29487593/transglycosylated-starch-modulates-the-gut-microbiome-and-expression-of-genes-related-to-lipid-synthesis-in-liver-and-adipose-tissue-of-pigs
#5
Monica A Newman, Renée M Petri, Dietmar Grüll, Qendrim Zebeli, Barbara U Metzler-Zebeli
Dietary inclusion of resistant starches can promote host health through modulation of the gastrointestinal microbiota, short-chain fatty acid (SCFA) profiles, and lipid metabolism. This study investigated the impact of a transglycosylated cornstarch (TGS) on gastric, ileal, cecal, proximal-colonic, and mid-colonic bacterial community profiles and fermentation metabolites using a growing pig model. It additionally evaluated the effect of TGS on the expression of host genes related to glucose and SCFA absorption, incretins, and satiety in the gut as well as host genes related to lipid metabolism in hepatic and adipose tissue...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29466062/management-of-diabetes-during-air-travel-a-systematic-literature-review-of-current-recommendations-and-their-supporting-evidence
#6
James Pavela, Rahul Suresh, Rebecca S Blue, Charles H Mathers, L Maria Belalcazar
OBJECTIVE: Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research. METHODS: A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included...
February 2018: Endocrine Practice
https://www.readbyqxmd.com/read/29461566/nya-glukoss%C3%A3-nkande-l%C3%A3-kemedel-%C3%A3-r-kardiovaskul%C3%A3-rt-s%C3%A3-kra-enstaka-diabetesl%C3%A3-kemedel-har-%C3%A3-ven-visats-skydda-mot-kardiovaskul%C3%A3-ra-och-renala-komplikationer
#7
Eva Toft, Mikael Rydén
Do novel therapies in type 2 diabetes have protective effects on cardiovascular and renal complications? A number of new antidiabetic drug classes have been introduced on the market in the last decade. Regulatory authorities have required that their safety in type 2 diabetes populations with high cardiovascular risk must be assessed. Consequently, a large number of outcome studies have been initiated, several of which have been published in recent years. Overall, this has so far shown that long-acting insulin analogues, DPP4-inhibitors, GLP1-receptor agonists and SGLT2-inhibitors are safe...
February 20, 2018: Läkartidningen
https://www.readbyqxmd.com/read/29450114/flavonoid-rich-extract-of-chromolaena-odorata-modulate-circulating-glp-1-in-wistar-rats-computational-evaluation-of-tgr5-involvement
#8
Olaposi Idowu Omotuyi, Oyekanmi Nash, Olumide Kayode Inyang, Joyce Ogidigo, Ojochenemi Enejoh, Okiemute Okpalefe, Tsuyoshi Hamada
Chromolaena odorata is a major bio-resource in folkloric treatment of diabetes. In the present study, its anti-diabetic component and underlying mechanism were investigated. A library containing 140 phytocompounds previously characterized from C. odorata was generated and docked (Autodock Vina) into homology models of dipeptidyl peptidase (DPP)-4, Takeda-G-protein-receptor-5 (TGR5), glucagon-like peptide 1 (GLP1) receptor, renal sodium dependent glucose transporter (SGLUT)-1/2 and nucleotide-binding oligomerization domain (NOD) proteins 1&2...
February 2018: 3 Biotech
https://www.readbyqxmd.com/read/29416857/glp1-and-gip-are-involved-in-the-action-of-synbiotics-in-broiler-chickens
#9
Pawel Antoni Kolodziejski, Maciej Sassek, Daniela Chalupka, Natalia Leciejewska, Leszek Nogowski, Pawel Mackowiak, Damian Jozefiak, Katarzyna Stadnicka, Maria Siwek, Marek Bednarczyk, Tomasz Szwaczkowski, Ewa Pruszynska-Oszmalek
Background: In order to discover new strategies to replace antibiotics in the post-antibiotic era in meat-type chicken production, two new synbiotics were tested: (Lactobacillus salivarius IBB3154 plus galactooligosaccharide (Syn1) and Lactobacillus plantarum IBB3036 plus raffinose family oligosaccharides (Syn2). Methods: The synbiotics were administered via syringe, using a special automatic system, into the egg air chamber of Cobb 500 broiler chicks on the 12th day of egg incubation (2 mg of prebiotics + 105 cfu bacteria per egg)...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29416634/loss-of-epithelium-specific-gpx2-results-in-aberrant-cell-fate-decisions-during-intestinal-differentiation
#10
Claudia Lennicke, Jette Rahn, Claudia Wickenhauser, Rudolf Lichtenfels, Andreas S Müller, Ludger A Wessjohann, Anna P Kipp, Barbara Seliger
The selenoprotein glutathione peroxidase 2 (GPx2) is expressed in the epithelium of the gastrointestinal tract, where it is thought to be involved in maintaining mucosal homeostasis. To gain novel insights into the role of GPx2, proteomic profiles of colonic tissues either derived from wild type (WT) or GPx2 knockout (KO) mice, maintained under selenium (Se) deficiency or adequate Se supplementation conditions were established and analyzed. Amongst the panel of differentially expressed proteins, the calcium-activated chloride channel regulator 1 (CLCA1) was significantly down-regulated in GPx2 KO versus WT mice regardless of the given Se status...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29412812/intestinal-peptide-changes-after-bariatric-and-minimally-invasive-surgery-relation-to-diabetes-remission
#11
REVIEW
Lidia Castagneto Gissey, James Casella Mariolo, Geltrude Mingrone
Bariatric surgery is very effective in achieving and maintaining weight loss but it is also associated with improvement of obesity metabolic complications, primarily type 2 diabetes (T2D). Remission of T2D or at least a net improvement of glycemic control persists for at least 5 years. The bypass of duodenum and of the first portion of the jejunum up to the Treitz ligament as in Roux-en-Y Gastric Bypass (RYGB), or the bypass of the duodenum, the entire jejunum and the first tract of the ileum, such as in Bilio-Pancreatic Diversion (BPD), achieve different results on insulin sensitivity...
February 2018: Peptides
https://www.readbyqxmd.com/read/29409957/dpp-4-is-expressed-in-human-pancreatic-beta-cells-and-its-direct-inhibition-improves-beta-cell-function-and-survival-in-type-2-diabetes
#12
Marco Bugliani, Farooq Syed, Flavia M M Paula, Bilal A Omar, Mara Suleiman, Sandra Mossuto, Francesca Grano, Francesco Cardarelli, Ugo Boggi, Fabio Vistoli, Franco Filipponi, Paolo De Simone, Lorella Marselli, Vincenzo De Tata, Bo Ahren, Decio L Eizirik, Piero Marchetti
It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells from non-diabetic (ND) and type 2 diabetic (T2D) individuals, including the effects of its inhibition on beta cell function and survival. Isolated islets were prepared from 25 ND and 18 T2D organ donors; studies were also performed with the human insulin-producing EndoC-βH1 cells...
January 31, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29378946/method-to-generate-highly-stable-d-amino-acid-analogs-of-bioactive-helical-peptides-using-a-mirror-image-of-the-entire-pdb
#13
Michael Garton, Satra Nim, Tracy A Stone, Kyle Ethan Wang, Charles M Deber, Philip M Kim
Biologics are a rapidly growing class of therapeutics with many advantages over traditional small molecule drugs. A major obstacle to their development is that proteins and peptides are easily destroyed by proteases and, thus, typically have prohibitively short half-lives in human gut, plasma, and cells. One of the most effective ways to prevent degradation is to engineer analogs from dextrorotary (D)-amino acids, with up to 105 -fold improvements in potency reported. We here propose a general peptide-engineering platform that overcomes limitations of previous methods...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29368965/consensus-statement-by-the-american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-on-the-comprehensive-type-2-diabetes-management-algorithm-2018-executive-summary
#14
Alan J Garber, Martin J Abrahamson, Joshua I Barzilay, Lawrence Blonde, Zachary T Bloomgarden, Michael A Bush, Samuel Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Vivian A Fonseca, Jeffrey R Garber, W Timothy Garvey, George Grunberger, Yehuda Handelsman, Irl B Hirsch, Paul S Jellinger, Janet B McGill, Jeffrey I Mechanick, Paul D Rosenblit, Guillermo E Umpierrez
A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial...
January 2018: Endocrine Practice
https://www.readbyqxmd.com/read/29367876/insulinoma-presenting-with-post-prandial-hypoglycaemia-following-fundoplication
#15
Sarah Y Qian, Matthew J L Hare, Alan Pham, Duncan J Topliss
Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68 Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29357131/structure-and-function-of-bone-marrow-adipocytes
#16
Francisco José Albuquerque de Paula, Clifford J Rosen
Adipocytes are heterogeneous cells strongly linked to energy storage and disposal. In parallel, adipocytes are endowed with an extensive portfolio of endocrine molecules, whose secretion varies depending on nutritional status. Marrow adipose tissue (MAT) has specific characteristics that are not shared by white (WAT) or brown (BAT) adipose tissue. First, marrow adipocytes and osteoblasts are terminally differentiated cells that originate from the same bone marrow mesenchymal stromal cell. Differently from WAT adipocytes, marrow adipocytes expand under conditions of energy restriction and seem to be not influenced by energy surplus, at least in humans...
December 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/29299622/a-novel-galactolipase-from-a-green-microalga-chlorella-kessleri-purification-characterization-molecular-cloning-and-heterologous-expression
#17
Shuhei Hashiro, Koyu Fujiuchi, Daisuke Sugimori, Hisashi Yasueda
We have identified an enzyme, galactolipase (ckGL), which hydrolyzes the acyl ester bond of galactolipids such as digalactosyldiacylglycerol (DGDG), in the microalga Chlorella kessleri. Following purification of the enzyme to electrophoretic homogeneity from cell-free extract, the maximum activity toward DGDG was observed at pH 6.5 and 37 °C. ckGL was Ca2+ -dependent enzyme and displayed an apparent molecular mass of approx. 53 kDa on SDS-PAGE. The substrate specificity was in the order: DGDG (100%) > monogalactosyldiacylglycerol ≈ phosphatidylglycerol (~ 40%) > sulfoquinovosyldiacylglycerol (~ 20%); the enzyme exhibited almost no activity toward glycerides and other phospholipids...
February 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29192276/protein-lysine-methyltransferases-g9a-and-glp1-promote-responses-to-dna-damage
#18
Vasudeva Ginjala, Lizahira Rodriguez-Colon, Bratati Ganguly, Prawallika Gangidi, Paul Gallina, Husam Al-Hraishawi, Atul Kulkarni, Jeremy Tang, Jinesh Gheeya, Srilatha Simhadri, Ming Yao, Bing Xia, Shridar Ganesan
Upon induction of DNA breaks, ATM activation leads to a cascade of local chromatin modifications that promote efficient recruitment of DNA repair proteins. Errors in this DNA repair pathway lead to genomic instability and cancer predisposition. Here, we show that the protein lysine methyltransferase G9a (also known as EHMT2) and GLP1 (also known as EHMT1) are critical components of the DNA repair pathway. G9a and GLP1 rapidly localizes to DNA breaks, with GLP1 localization being dependent on G9a. ATM phosphorylation of G9a on serine 569 is required for its recruitment to DNA breaks...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29165354/the-role-of-glucagon-like-peptide-1-glp1-in-type-3-diabetes-glp-1-controls-insulin-resistance-neuroinflammation-and-neurogenesis-in-the-brain
#19
REVIEW
Choon Sang Bae, Juhyun Song
Alzheimer's disease (AD), characterized by the aggregation of amyloid-β (Aβ) protein and neuroinflammation, is the most common neurodegenerative disease globally. Previous studies have reported that some AD patients show impaired glucose utilization in brain, leading to cognitive decline. Recently, diabetes-induced dementia has been called "type 3 diabetes", based on features in common with those of type 2 diabetes and the progression of AD. Impaired glucose uptake and insulin resistance in the brain are important issues in type 3 diabetes, because these problems ultimately aggravate memory dysfunction in the brain...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29135080/comparison-of-medication-adherence-and-persistence-in-type-2-diabetes-a-systematic-review-and-meta-analysis
#20
Andrew McGovern, Zayd Tippu, William Hinton, Neil Munro, Martin Whyte, Simon de Lusignan
Limited medication adherence and persistence with treatment are barriers to successful management of type 2 diabetes (T2D). We searched MEDLINE, EMBASE, the Cochrane Library, the Register of Controlled Trials, PsychINFO and CINAHL for observational and interventional studies that compared the adherence or persistence associated with 2 or more glucose-lowering medications in people with T2D. Where 5 or more studies provided the same comparison, a random-effects meta-analysis was performed, reporting mean difference (MD) or odds ratio (OR) for adherence or persistence, depending on the pooled study outcomes...
April 2018: Diabetes, Obesity & Metabolism
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