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GLP1, kidney

Peter Ueda, Henrik Svanström, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak
OBJECTIVE: To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern. DESIGN: Register based cohort study. SETTING: Sweden and Denmark from July 2013 to December 2016. PARTICIPANTS: A propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists...
November 14, 2018: BMJ: British Medical Journal
Da Guo, Kai Yu, Xin-Yuan Sun, Jian-Ming Ouyang
Natural Gracilaria lemaneiformis sulfated polysaccharide (GLP0, molecular weight = 622 kDa) was degraded by H2 O2 to obtain seven degraded fragments, namely, GLP1, GLP2, GLP3, GLP4, GLP5, GLP6, and GLP7, with molecular weights of 106, 49.6, 10.5, 6.14, 5.06, 3.71, and 2.42 kDa, respectively. FT-IR and NMR results indicated that H2 O2 degradation does not change the structure of GLP polysaccharides, whereas the content of the characteristic -OSO3 H group (13.46% ± 0.10%) slightly increased than that of the natural polysaccharide (13...
2018: Oxidative Medicine and Cellular Longevity
Monica Wang
No abstract text is available yet for this article.
October 2018: Nature Reviews. Nephrology
Fuyong Du, Simon A Hinke, Cassandre Cavanaugh, David Polidori, Nathanial Wallace, Thomas Kirchner, Matthew Jennis, Wensheng Lang, Gee-Hong Kuo, Micheal D 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 inhibition in patients with type 2 diabetes. However, questions remain about altered gastrointestinal (GI) luminal glucose and tolerability, and this was evaluated in slc5a1-/- mice or with a potent dual inhibitor (compound 8; SGLT1 K i = 1.5 ± 0.5 nM 100-fold greater potency than phlorizin; SGLT2 K i = 0.4 ± 0...
June 2018: Journal of Pharmacology and Experimental Therapeutics
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
Marianna Papademetriou, Vasilios G Athyros, Eleni Geladari, Michael Doumas, Costas Tsioufis, Vasilios Papademetriou
Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease. NAFLD may evolve to non-alcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD) mortality. There is no generally accepted effective treatment for NAFLD/NASH. Chronic kidney disease (CKD) is relatively common and might co-exist with NAFLD/NASH, aggravate one another, and increase CVD risk. Common therapies could improve outcome. Potent statins at high doses, such as atorvastatin and rosuvastatin, ameliorate NAFLD/NASH and reduce the mortality rates by half as compared with those on the same statins but without liver disease and CVD-related events are reduced by atorvastatin for patients with all stages of CKD...
2018: Current Vascular Pharmacology
Kirsi Mikkola, Cheng-Bin Yim, Paula Lehtiniemi, Saila Kauhanen, Miikka Tarkia, Tuula Tolvanen, Pirjo Nuutila, Olof Solin
BACKGROUND: Several radiometal-labeled, exendin-based tracers that target glucagon-like peptide-1 receptors (GLP-1R) have been intensively explored for β cell imaging. The main obstacle has been the high uptake of tracer in the kidneys. This study aimed to develop a novel GLP1-R-specific tracer, with fluorine-18 attached to exendin-4, to label β cells for clinical imaging with PET (positron emission tomography). We hypothesized that this tracer would undergo reduced kidney uptake. (18)F-labeled [Nle(14),Lys(40)]exendin-4 analog ([(18)F]exendin-4) was produced via Cu-catalyzed click chemistry...
December 2016: EJNMMI Research
Ivo Quack, Ralf Westenfeld
Patients with kidney disease have a significantly increased cardiovascular morbidity and mortality. Especially diabetics have an increased risk to develop renal insufficiency and cardiovascular events. Two recent studies show that the SGLT2 inhibitor Empagliflozin and the GLP1 agonist Liraglutid are able to lower the cardiovascular risk of type2 diabetics with renal insufficiency. Recent observations suggest that bradycardia and asystole are main triggers for sudden cardiac death in patients with chronic kidney disease...
November 2016: Deutsche Medizinische Wochenschrift
Carlo Garofalo, Nicolangelo Iazzetta, Andrea Camocardi, Mario Pacilio, Carmela Iodice, Roberto Minutolo, Luca De Nicola, Giuseppe Conte
Diabetes mellitus (DM) is the most important non-communicable disease after hypertension. Prevalence of type 2 DM has progressively increased over the last decades. In Italy, 11.8% of the general adult population can be identified as diabetic. The major complication of DM is diabetic nephropathy (DM-CKD), which develops in approximately one-third of diabetics. Achieving optimal glycemic control is the first therapeutic goal in the management of DM-CKD. In recent years, new antidiabetic drugs have been marketed (GLP1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors) to ameliorate glycemia in patients nave or treated by means of traditional agents, such as sulfonylureas, metformin, glinides, insulin...
September 2015: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Ron L Bonaccorso, Oleg G Chepurny, Christoph Becker-Pauly, George G Holz, Robert P Doyle
Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R)...
September 8, 2015: Molecular Pharmaceutics
Xubiao Liao, Lawei Yang, Meizhen Chen, Jie Yu, Shumeng Zhang, Yaoyao Ju
Gracilaria lemaneiformis is cultivated on a large scale in China for industrial production of agarose, a natural polysaccharide, which has been shown to have many beneficial bioactivities such as antitumor, antiviral antioxidant activities, etc. In the present study, the hypoglycemic and antioxidant effects of a polysaccharide extracted from Gracilaria lemaneiformis (GLP; Mw, 121.89 kDa) and its chemically degraded products (GLP1 and GLP2: Mw, 57.02 and 14.29 kDa, respectively) were investigated in alloxan-induced diabetic mice...
August 2015: Food & Function
Alena Adamíková
The incretin hormone GLP1 (glucagon-like peptide 1) has also systemic effects besides its effects on the pancreas. The renal expression for the receptors GLP1 and DPP4 has been described in a whole line of experimental stu-dies. Activation of the receptors for GLP1 in the kidneys has diuretic and natriuretic effects apparently through the renal tubular cells and sodium transporters. Pre-clinical incretin therapy decreased albuminuria, affected glomerulosclerosis, oxidative stress and fibrosis in the kidneys...
April 2015: Vnitr̆ní Lékar̆ství
Gerald H Tomkin
In recent years the treatment focus for type 2 diabetes has shifted to prevention by lifestyle change and to more aggressive reduction of blood sugars during the early stage of treatment. Weight reduction is an important goal for many people with type 2 diabetes. Bariatric surgery is no longer considered a last resort treatment. Glucagon-like peptide-1 agonists given by injection are emerging as a useful treatment since they not only lower blood sugar but are associated with a modest weight reduction. The role of the oral dipeptidyl peptidase 4 inhibitors is emerging as second line treatment ahead of sulphonylureas due to a possible beneficial effect on the beta cell and weight neutrality...
October 15, 2014: World Journal of Diabetes
Mohamed Lotfy, Jaipaul Singh, Hameed Rashed, Saeed Tariq, Erika Zilahi, Ernest Adeghate
Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes, employing four groups of ten rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 μg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time PCR to examine the expression of genes...
March 2014: Journal of Endocrinology
Vishal Gupta
Drugs that augment the incretin system [glucagon like peptide (GLP) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors] represent a novel class of anti-hyperglycemic agents that have shown to improve the health and survival of beta-cells (improvement in postprandial hyperglycemia) and suppress glucagon (improvement in fasting hyperglycemia). The incretins represent a large family of molecules referred to as the "glucagon superfamily of peptide hormones" of which more than 90% of the physiological effects of incretins are accomplished by GLP-1(7-37) and GLP1(7-36) amide and gastric insulinotropic peptide (GIP)...
March 2012: Indian Journal of Endocrinology and Metabolism
D Krakow, E Sebald, L M King, D H Cohn
We report the isolation, genomic structure, chromosomal location, and expression pattern of the FEM1A gene, the human ortholog of the Caenorhabditis elegans fem-1 and mouse Fem1a genes. The coding sequence is 1851 bp and encodes a 617 amino acid protein. The human FEM1A protein has 65% identity with the mouse Fem1a protein and 34% identity with the C. elegans fem-1 protein, indicating conservation of this protein. The N-terminal region of the encoded protein contains six ankyrin repeat elements, a motif found in signaling and transcriptional regulatory molecules such as Notch and glp1...
November 28, 2001: Gene
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