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https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#1
Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W Dong, Franck Mauvais-Jarvis, Vivian A Fonseca, Hongju Wu
Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#2
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/28761216/use-of-canagliflozin-in-combination-with-and-compared-to-incretin-based-therapies-in-type-2-diabetes
#3
Richard E Pratley, Eugenio Cersosimo
In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1 [GLP-1] receptor agonists) are widely used to treat patients with type 2 diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor, has demonstrated superior A1C lowering compared to the DPP-4 inhibitor sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood pressure reduction. The addition of canagliflozin to treatment regimens that include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further improve glycemic control, while still maintaining beneficial effects on cardiometabolic parameters such as body weight and blood pressure...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28750074/dpp4-gene-variation-affects-glp-1-secretion-insulin-secretion-and-glucose-tolerance-in-humans-with-high-body-adiposity
#4
Anja Böhm, Robert Wagner, Fausto Machicao, Jens Juul Holst, Baptist Gallwitz, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF)...
2017: PloS One
https://www.readbyqxmd.com/read/28746743/the-incretin-concept-revised-the-origin-of-glp-1-s-insulinotropic-function-the-gut-the-islets-or-both
#5
Daisuke Yabe, Yusuke Seino, Yutaka Seino
Incretins comprise a pair of gut hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted in response to food ingestion and enhance glucose-dependent insulin secretion (GIIS) from pancreatic β-cells. Immediately after secretion, GLP-1 is degraded by dipeptidyl peptidase-4 (DPP-4) more rapidly than GIP, and circulating levels of biologically intact GLP-1 are substantially lower than those of biologically intact GIP. Therefore, there has been a debate on how the gut-derived GLP-1 exerts insulinotropic actions...
July 26, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28743778/fracture-risk-associated-with-common-medications-used-in-treating-type-2-diabetes-mellitus
#6
Daniel Wolverton, Melissa M Blair
PURPOSE: Published data on the risk of bone fractures associated with medications used for the treatment of type 2 diabetes mellitus are summarized. SUMMARY: A systematic literature search identified 108 publications on controlled trials and 6 meta-analyses addressing the potential for fractures with the use of 7 commonly used antidiabetic classes: thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, biguanides, insulin, and sulfonylureas...
August 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28741456/effects-of-oral-and-non-insulin-injectable-antidiabetic-treatment-in-hypertension-a-systematic-review
#7
Vasiliki Katsi, Georgios Georgiopoulos, Georgia Vogiatzi, Dimitrios Oikonomou, Maria Megapanou, John Skoumas, Charalampos Vlachopoulos, Petros Nihoyannopoulos, Dimitris Tousoulis
BACKGROUND: Diabetes mellitus type 2 (T2DM) often co-exists with hypertension, and this aggregation of co-morbidities amplifies the risk for future cardiovascular events. Therefore, it appears crucial to understand the essence of choosing oral and non-insulin injectable anti-diabetic drugs (ADs) with a favorable hemodynamic impact that could partially attenuate the increased baseline cardiovascular risk. OBJECTIVE: We sought to evaluate the effect of ADs on blood pressure (BP) indices and to assess the potential role of certain ADs towards hypertension treatment...
May 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28725624/incretin-effect-of-urena-lobata-leaves-extract-on-structure-and-function-of-rats-islet-%C3%AE-cells
#8
Y Purnomo, D W Soeatmadji, S B Sumitro, M A Widodo
This study aims to determine the incretin effects of Urena lobata leaves extract on the structure and function of rats islet β-cells. This study utilizes male Sprague-Dawley rats divided into 2 control group and 3 test group (n = 5). Diabetic rats were induced with High Fructose Diet (HFD) and single dose intraperitoneal streptozotocin 25 mg/kg bw. Aqueous leaves extract of U. lobata was prepared by decoction methods and administrated orally with doses of 250, 500, and 1000 mg/kg bw for 4 weeks then incretin effect was evaluated by measuring serum GLP-1, insulin, and blood glucose levels...
July 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#9
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28699892/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#10
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28664354/impact-of-medicine-withdrawal-on-reporting-of-adverse-events-involving-therapeutic-alternatives-a-study-from-the-french-spontaneous-reporting-database
#11
Cécile Pageot, Julien Bezin, Andy Smith, Mickael Arnaud, Francesco Salvo, Françoise Haramburu, Bernard Bégaud, Antoine Pariente
INTRODUCTION: The consequences of the withdrawal of marketing authorisation of drugs have mostly been studied considering drug prescription patterns for the therapeutic alternatives of the withdrawn drugs. The potential concomitant changes in the reporting of adverse reactions concerning these alternatives have been studied less often. OBJECTIVE: The objective of this study was to analyse the changes in the reporting of adverse events (AEs) for therapeutic alternatives after the withdrawal of three medicines (dextropropoxyphene, pioglitazone and tetrazepam) from the market for safety reasons...
June 29, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-nonalcoholic-steatohepatitis-and-liver-fibrosis
#12
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis, and increased cardiovascular mortality. Dipeptidyl peptidase-4 inhibitors (gliptins) are indirect glucagon-like peptide 1 agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
July 25, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28630262/dipeptidyl-peptidase-4-inhibitor-anagliptin-prevents-intracranial-aneurysm-growth-by-suppressing-macrophage-infiltration-and-activation
#13
Taichi Ikedo, Manabu Minami, Hiroharu Kataoka, Kosuke Hayashi, Manabu Nagata, Risako Fujikawa, Sei Higuchi, Mika Yasui, Tomohiro Aoki, Miyuki Fukuda, Masayuki Yokode, Susumu Miyamoto
BACKGROUND: Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin...
June 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28600546/dipeptidyl-peptidase-4-and-adolescent-idiopathic-scoliosis-expression-in-osteoblasts
#14
Emilie Normand, Anita Franco, Alain Moreau, Valérie Marcil
It has been proposed that girls with adolescent idiopathic scoliosis (AIS) tend to have a taller stature and a lower body mass index. Energy homeostasis, that is known to affect bone growth, could contribute to these characteristics. In circulation, dipeptidyl peptidase-4 (DPP-4) inactivates glucagon-like peptide-1 (GLP-1), an incretin that promotes insulin secretion and sensitivity. Our objectives were to investigate DPP-4 status in plasma and in osteoblasts of AIS subjects and controls and to evaluate the regulatory role of metabolic effectors on DPP-4 expression...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28599244/cb-1r-and-glp-1r-gene-expressions-and-oxidative-stress-in-the-liver-of-diabetic-rats-treated-with-sitagliptin
#15
Zeynep Mine Coskun, Meral Koyuturk, Sezin Karabulut, Sema Bolkent
BACKGROUND: Type 2 diabetes is a major health problem affecting millions of people. Controlled eating and regular physical activity are important for the management of type 2 diabetes. Dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor sitagliptin is a potent agent for the treatment of type-2 diabetes. The aim of this study was to examine the effects of sitagliptin on the liver of rats with streptozotocin (STZ)-induced diabetes, in terms of (i) the expression levels of the cannabinoid 1 receptor (CB-1R) and glucagon-like peptide 1 receptor (GLP-1R), (ii) alterations in the number and localization of these peptides, and (iii) changes in histological and oxidative damage...
March 20, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28596247/incretin-based-treatments-and-mortality-in-patients-with-type-2-diabetes-systematic-review-and-meta-analysis
#16
REVIEW
Jiali Liu, Ling Li, Ke Deng, Chang Xu, Jason W Busse, Per Olav Vandvik, Sheyu Li, Gordon H Guyatt, Xin Sun
Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.Eligibility criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes...
June 8, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28593550/yh18421-a-novel-gpr119-agonist-exerts-sustained-glucose-lowering-and-weight-loss-in-diabetic-mouse-model
#17
Yoo Hoi Park, Hyun Ho Choi, Dong Hoon Lee, Soo Yong Chung, Na Yeon Yang, Do Hoon Kim, Mi Kyeong Ju, Tae Dong Han, Su Youn Nam, Kyu-Won Kim
G-protein-coupled receptor 119 (GPR119) represents a promising target for the treatment of type 2 diabetes as it can increase both GLP-1 secretion from intestinal L cells and glucose-stimulated insulin secretion (GSIS) from pancreatic β cells. Due to this dual mechanism of action, the development of small molecule GPR119 agonists has received much interest for the treatment of type 2 diabetes. Here, we identified a novel small-molecule GPR119 agonist, YH18421 and evaluated its therapeutic potential. YH18421 specifically activated human GPR119 with high potency and potentiated GLP-1 secretion and GSIS in vitro cell based systems...
June 8, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28579834/hypoglycemia-a-review-of-definitions-used-in-clinical-trials-evaluating-antihyperglycemic-drugs-for-diabetes
#18
REVIEW
Chakrapani Balijepalli, Eric Druyts, Gaye Siliman, Michel Joffres, Kristian Thorlund, Edward J Mills
OBJECTIVE: To understand the severity and potential impact of heterogeneity in definitions of hypoglycemia used in diabetes research, we aimed to review the hypoglycemia definitions adopted in randomized controlled trials (RCTs). METHODS: We reviewed 109 RCTs included in the Canadian Agency for Drugs and Technologies in Health reports for the second- and third-line therapy for the patients with type 2 diabetes (T2D). RESULTS: Nearly 60% (n=66) of the studies reviewed presented the definitions for overall hypoglycemia, and another 20% (n=22) of the studies reported the results for hypoglycemia but did not report a definition...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28579289/effects-of-anti-somatostatin-agents-on-glucose-metabolism
#19
REVIEW
B Vergès
The anti-somatostatin agents used to treat acromegaly, Cushing's disease and neuroendocrine tumours also have hyperglycaemic effects. This is particularly true for pasireotide. Hyperglycaemic events are seen in 57-73% of patients with Cushing's treated with pasireotide, with a need to initiate antidiabetic treatment in about 50% of these patients. In acromegaly, treatment with pasireotide induces hyperglycaemia in 29-61% of patients. Pasireotide-induced hyperglycemia occurs early, within the first 3 months of treatment, due to a decrease in insulin secretion secondary to a fall in secretion of GLP-1 and GIP, and potentially also due to a direct inhibitory effect of pasireotide on beta cells...
June 1, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28544214/do-we-know-the-true-mechanism-of-action-of-the-dpp-4-inhibitors
#20
REVIEW
Emilie Skytte Andersen, Carolyn F Deacon, Jens Juul Holst
The prevalence of type 2 diabetes is increasing which is alarming because of its serious complications. Antidiabetic treatment aims to control glucose homeostasis as tightly as possible in order to reduce these complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a recent addition to the antidiabetic treatment modalities, and have become widely accepted because of their good efficacy, their benign side effect profile and their low hypoglycaemia risk. The actions of DPP-4 inhibitors are not direct, but rather are mediated indirectly through preservation of the substrates they protect from degradation...
May 24, 2017: Diabetes, Obesity & Metabolism
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