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https://www.readbyqxmd.com/read/29241374/pharmacokinetic-drug-evaluation-of-empagliflozin-plus-linagliptin-for-the-treatment-of-type-2-diabetes
#1
C V Rizos, T D Filippatos, M S Elisaf
Type 2 diabetes mellitus has become a growing epidemic and therefore efficient treatment strategies that target its management are needed. The treatment of diabetic patients often requires the combination of antidiabetic drug classes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) block glucose reabsorption in the proximal renal tubules. Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glucose metabolism by blocking the enzyme that degrades incretins leading to increased insulin secretion. Areas covered: The aim of the review is to present the available data on pharmacokinetic properties/pharmacodynamics, metabolic and cardiovascular effects...
December 15, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#2
Michael Gejl, Birgitte Brock, Lærke Egefjord, Kim Vang, Jørgen Rungby, Albert Gjedde
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233907/glucagon-like-peptide-1-acutely-affects-renal-blood-flow-and-urinary-flow-rate-in-spontaneously-hypertensive-rats-despite-significantly-reduced-renal-expression-of-glp-1-receptors
#3
Jonas Ronn, Elisa P Jensen, Nicolai J Wewer Albrechtsen, Jens Juul Holst, Charlotte M Sorensen
Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29227582/role-of-the-sodium-hydrogen-exchanger-in-mediating-the-renal-effects-of-drugs-commonly-used-in-the-treatment-of-type-2-diabetes
#4
REVIEW
Milton Packer
Diabetes is characterized by an increased activity of the sodium-hydrogen exchanger (NHE) in the glomerulus and renal tubules, which contributes importantly to the development of nephropathy. Despite the established role played by the exchanger in experimental studies, it has not been specifically targeted by those seeking to develop novel pharmacological treatments for diabetes. This review demonstrates that many existing drugs that are commonly prescribed to patients with diabetes act on the NHE1 and NHE3 isoforms in the kidney...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29227575/effect-of-a-single-dose-of-the-dpp-4-inhibitor-sitagliptin-on-%C3%AE-cell-function-and-incretin-hormone-secretion-after-meal-ingestion-in-healthy-volunteers-and-drug-na%C3%A3-ve-well-controlled-type-2-diabetes-subjects
#5
Wathik Alsalim, Olga Göransson, Richard D Carr, Roberto Bizzotto, Andrea Tura, Giovanni Pacini, Andrea Mari, Bo Ahrén
To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, twelve healthy- and twelve drug naïve well-controlled type 2 diabetes subjects (T2D; mean HbA1c 43 mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525 kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate)...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29226618/enteroinsular-hormones-in-two-siblings-with-donohue-syndrome-and-complete-leptin-deficiency
#6
M Güemes, S A Rahman, P Shah, K Hussain
The main biochemical hallmark of the rare and lethal condition of Donohue syndrome (DS) is hyperinsulinemia. The roles of the gut and other pancreatic hormones involved in glucose metabolism, satiety and energy expenditure have not been previously reported in DS. Two siblings with genetically confirmed DS and extremely low weight underwent a mixed meal (MM) test where pancreatic hormones insulin, C-peptide, glucagon, active amylin, pancreatic polypeptide (PP) as well as gut hormones active glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, peptide YY (PYY) and leptin were analyzed using a Multiplex assay...
December 11, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/29226105/non-alcoholic-fatty-liver-disease-a-clinical-update
#7
REVIEW
Joseph M Pappachan, Shithu Babu, Babu Krishnan, Nishal C Ravindran
Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries because of the obesity epidemic. The disease increases liver-related morbidity and mortality, and often increases the risk for other comorbidities, such as type 2 diabetes and cardiovascular disease. Insulin resistance related to metabolic syndrome is the main pathogenic trigger that, in association with adverse genetic, humoral, hormonal and lifestyle factors, precipitates development of NAFLD...
December 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29223646/exploring-the-effects-of-dpp-4-inhibitors-on-the-kidney-from-the-bench-to-clinical-trials
#8
REVIEW
Giuseppe Coppolino, Christian Leporini, Laura Rivoli, Francesco Ursini, Eugenio Donato di Paola, Valeria Cernaro, Franco Arturi, Davide Bolignano, Emilio Russo, Giovambattista De Sarro, Michele Andreucci
Dipeptidyl-peptidase-4 (DPP-4) inhibitors are a relatively new class of non-insulin glucose-lowering agents, belonging to the incretin family, which are able to improve glycemic control with a favorable safety profile, since they are associated with a low risk of hypoglycemia, no weight gain, and good tolerability in patients with chronic renal failure. Some experimental and clinical studies suggest that these drugs may exert significant pleiotropic effects, in particular on chronic kidney disease (CKD) progression, but data from clinical trials are still controversial...
December 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29222967/stimulation-of-the-endogenous-incretin-glucose-dependent-insulinotropic-peptide-by-enteral-dextrose-improves-glucose-homeostasis-and-inflammation-in-murine-endotoxemia
#9
Faraaz Ali Shah, Srikanth Singamsetty, Lanping Guo, Byron W Chuan, Sherie McDonald, Bryce A Cooper, Brett J O'Donnell, Darko Stefanovski, Burton Wice, Yingze Zhang, Christopher P O'Donnell, Bryan J McVerry
Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis...
November 21, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29195256/increased-postprandial-glucagon-like-peptide-1-glp-1-production-after-endoscopic-gastrointestinal-bypass-using-the-cousin-lumen-apposing-stent-in-a-porcine-model
#10
Robert Caiazzo, Julien Branche, Mehdi Daoudi, Gilles Solecki, Thomas Hubert, Audrey Quenon, Violeta Raverdy, François Cousin, François Henin, Valery Dalle, Stéphane Noel, Geoffroy Vanbiervliet, Marc Barthet, François Pattou
Background and study aims Endoscopic techniques have demonstrated their effectiveness in metabolic surgery, notably through a gastrointestinal (GI) liner, with a less invasive approach than conventional surgery. Our study evaluates the safety and efficacy of endoscopic GI anastomosis (EGIA) using a lumen-apposing stent to secure the anastomosis. Materials and methods EGIA was performed using the transgastric approach with a two-channel endoscope with a novel stent (Cousin Biotech). First, a safety study with a follow-up of 12 months was performed on five piglets...
December 1, 2017: Endoscopy
https://www.readbyqxmd.com/read/29193800/suppression-of-circadian-secretion-of-glucagon-like-peptide-1-by-the-saturated-fatty-acid-palmitate
#11
A Martchenko, R H Oh, S E Wheeler, P Gurges, J A Chalmers, P L Brubaker
AIM: Glucagon-like peptide-1 is an incretin hormone secreted by the intestinal L-cell with a circadian rhythm that parallels expression of the core clock gene, Bmal1. Although feeding rats a high-fat/high-sucrose Western diet impairs rhythmic glucagon-like peptide-1 release, the mechanisms underlying this effect remain unclear. Therefore, the aim of the present study was to determine the pathway(s) by which the saturated fat, palmitate, a major component of the Western diet, impairs circadian glucagon-like peptide-1 secretion...
November 29, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29193572/incretin-based-therapies-and-risk-of-pancreatic-cancer-in-patients-with-type-2-diabetes-a-meta-analysis-of-randomised-controlled-trials
#12
Haining Wang, Ye Liu, Qing Tian, Jin Yang, Ran Lu, Siyan Zhan, Jari Haukka, Tianpei Hong
AIMS: Conflicting evidence exists regarding the potential risk of pancreatic cancer with use of incretin drugs in patients with type 2 diabetes (T2DM). We performed a meta-analysis of randomised controlled trials (RCTs), including six recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with T2DM. MATERIALS AND METHODS: The PubMed, Embase, Cochrane Central Register and ClininalTrials...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29184702/pharmacological-inhibition-of-diacylglycerol-acyltransferase-1-and-insights-into-postprandial-gut-peptide-secretion
#13
Benjamin S Maciejewski, Tara B Manion, Claire M Steppan
AIM: To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) plays in postprandial gut peptide secretion and signaling. METHODS: The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge. Following a lipid challenge, plasma was collected via cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h. Incretin hormones [glucagon like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose dependent insulinotropic polypeptide (GIP)] were then quantitated...
November 15, 2017: World Journal of Gastrointestinal Pathophysiology
https://www.readbyqxmd.com/read/29182565/ppar%C3%AE-modulates-long-chain-fatty-acid-processing-in-the-intestinal-epithelium
#14
Kalina Duszka, Matej Oresic, Cedric Le May, Jürgen König, Walter Wahli
Nuclear receptor PPARγ affects lipid metabolism in several tissues, but its role in intestinal lipid metabolism has not been explored. As alterations have been observed in the plasma lipid profile of ad libitum fed intestinal epithelium-specific PPARγ knockout mice (iePPARγKO), we submitted these mice to lipid gavage challenges. Within hours after gavage with long chain unsaturated fatty acid (FA)-rich canola oil, the iePPARγKO mice had higher plasma free FA levels and lower gastric inhibitory polypeptide levels than their wild-type (WT) littermates, and altered expression of incretin genes and lipid metabolism-associated genes in the intestinal epithelium...
November 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29180017/role-of-osteopontin-and-its-regulation-in-pancreatic-islet
#15
Mengyin Cai, Pradeep Bompada, Albert Salehi, Juan R Acosta, Rashmi B Prasad, David Atac, Markku Laakso, Leif Groop, Yang De Marinis
Osteopontin (OPN) is involved in various physiological processes and also implicated in multiple pathological states. It has been suggested that OPN may have a role in type 2 diabetes (T2D) by protecting pancreatic islets and interaction with incretins. However, the regulation and function of OPN in islets, especially in humans, remains largely unexplored. In this study, we performed our investigations on both diabetic mouse model SUR1-E1506K+/+ and islets from human donors. We demonstrated that OPN protein, secretion and gene expression was elevated in the diabetic SUR1-E1506K+/+ islets...
November 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29175324/lixisenatide-reduces-amyloid-plaques-neurofibrillary-tangles-and-neuroinflammation-in-an-app-ps1-tau-mouse-model-of-alzheimer-s-disease
#16
Hong-Yan Cai, Jun-Ting Yang, Zhao-Jun Wang, Jun Zhang, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for Alzheimer's disease (AD). The impairment of insulin signaling has been found in AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises insulin signaling and acts as a neuroprotective growth factor. We have previously shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an important role in memory formation, synaptic plasticity and cell proliferation of rats. In the follow-up study, we analysed the neuroprotective effect and mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29171021/xenopus-glp-1-derived-and-pegylated-glp-1-receptor-agonists-long-acting-hypoglycemic-and-insulinotropic-activities-with-potential-therapeutic-utilities
#17
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Ying Zhang, Lin Liu, Junjie Fu
BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists are effective methods for treating type 2 diabetes. Numerous research efforts are focused on the development of long-acting GLP-1 receptor agonists. However, all GLP-1 receptor agonists in clinical use or in clinical development are based on human GLP-1 or Gila GLP-1. We previously identified xGLP-1B as a potent GLP-1 receptor agonist based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of xGLP-1B, alanine scanning was performed to study the structure-activity relationship of xGLP-1B...
November 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29168547/gastric-contractility-modulation-a-novel-method-for-the-treatment-of-type-2-diabetes-mellitus-and-obesity
#18
Jarosław Kozakowski, Harold E Lebovitz, Wojciech Zgliczyński, Wiesław Tarnowski
Because the majority of antidiabetic medications are of limited efficacy and patient compliance with treatment is usually poor, new therapies are still being searched for. In the review a newly developed system for treatment of subjects with type 2 diabetes and concomitant overweight/obesity is described. The system consists of an implantable pulse generator that delivers electrical stimuli through leads implanted in the sero-muscular layer of the stomach. The device recognises and automatically modulates natural electrical activity of the stomach during meals, strengthening gastric contractility...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/29168546/glucocorticoids-and-beta-cell-function
#19
Marta Fichna, Piotr Fichna
Glucocorticoids (GCs) play a pivotal role in carbohydrate metabolism. They counteract insulin by decreasing peripheral glucose uptake and stimulating hepatic gluconeogenesis, although they are best known for inducing insulin resistance (IR). Moreover, GCs may attenuate the incretin effect. Nevertheless, their direct impact on beta cells is not fully defined. This review aims to present the current understanding of this subject. Humans exposed to GC excess display IR, impaired glucose tolerance, and eventually develop diabetes...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/29162361/impaired-beta-cell-sensitivity-to-incretins-in-type-2-diabetes-is-insufficiently-compensated-by-higher-incretin-response
#20
A Tura, J I Bagger, E Ferrannini, J J Holst, F K Knop, T Vilsbøll, A Mari
BACKGROUND AND AIMS: The incretin effect is impaired in type 2 diabetes (T2D), but the underlying mechanisms are only partially understood. We investigated the relationships between the time course of the incretin effect and that of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) during oral glucose tolerance tests (OGTTs), thereby estimating incretin sensitivity of the beta cell, and its associated factors. METHODS AND RESULTS: Eight patients with T2D and eight matched subjects with normal glucose tolerance (NGT) received 25, 75, and 125 g OGTTs and corresponding isoglycemic glucose infusions (IIGI)...
October 13, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
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