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https://www.readbyqxmd.com/read/29683968/functional-correlation-between-the-pancreas-and-the-small-intestine-in-humans-the-first-evaluation-using-a-newly-developed-enteroscopy
#1
Daijuro Hayashi, Yoshiki Hirooka, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Takamichi Kuwahara, Manabu Kawai, Takeshi Yamamura, Kazuhiro Furukawa, Kohei Funasaka, Masanao Nakamura, Ryoji Miyahara, Osamu Watanabe, Masatoshi Ishigami, Senju Hashimoto, Hidemi Goto
OBJECTIVES: The aim of this study is to evaluate a functional correlation between the pancreas and the small intestine and the association of this relationship with nutritional status, using magnifying enteroscopy. METHODS: The subjects were adults aged 20 years or older who underwent upper gastrointestinal endoscopy. An endoscope was inserted into the jejunum, and 10% glucose was sprayed under magnifying observation to evaluate changes in blood flow in the villous capillary network...
April 19, 2018: Pancreas
https://www.readbyqxmd.com/read/29682682/molecular-and-clinical-roles-of-incretin-based-drugs-in-patients-with-heart-failure
#2
REVIEW
Bassant Orabi, Rasha Kaddoura, Amr S Omar, Cornelia Carr, Abdulaziz Alkhulaifi
Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors produce some beneficial and deleterious effects in diabetic patients not mediated by their glycemic lowering effects, and there is a need for better understanding of the molecular basis of these effects. They possess antioxidant and anti-inflammatory effects with some direct vasodilatory action (animal and human trial data) that may indirectly influence heart failure (HF). Unlike GLP-1R agonists, signaling for HF adverse effects was observed with two DPP-4 inhibitors, saxagliptin and alogliptin...
April 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29678908/the-lim-homeodomain-protein-isl1-mediates-the-function-of-tcf7l2-in-pancreatic-beta-cells
#3
Weijuan Shao, Vivian Szeto, Zhuolun Song, Lili Tian, Zhong-Ping Feng, Cristina M Nostro, Tianru Jin
Pancreatic β-cell Tcf7l2 deletion or its functional knockdown suggested the essential role of this Wnt pathway effector in controlling insulin secretion, glucose homeostasis, and β-cell gene expression. As the LIM homeodomain protein Isl1 is a suggested Wnt pathway downstream target, we hypothesize that it mediates metabolic functions of Tcf7l2. We aimed to determine the role of Isl1 in mediating the function of Tcf7l2 and the incretin hormone GLP-1 in pancreatic β-cells. Effect of dominant negative TCF7L2 (TCF7L2DN) mediated Wnt pathway functional knockdown on Isl1 expression was determined in βTCFDN mouse islets and in the rat insulinoma cell line INS-1 832/13...
April 20, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29673130/effects-of-gip-on-regional-blood-flow-during-normoglycemia-and-hyperglycemia-in-anesthetized-rats
#4
Xiang Gao, Andreas Lindqvist, Monica Sandberg, Leif Groop, Nils Wierup, Leif Jansson
The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects β-cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague-Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10-6 -10-12  mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29672742/older-subjects-with-%C3%AE-cell-dysfunction-have-an-accentuated-incretin-release
#5
José de Jesús Garduno-Garcia, Amalia Gastaldelli, Ralph A DeFronzo, Raweewan Lertwattanarak, Jens J Holst, Nicolas Musi
Objective: Insulin secretion declines with age and this contributes to the increased risk of developing impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older subjects. Insulin secretion is regulated by the incretin hormones glucagon-like peptide (GLP) 1 and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is reduced in older subjects, and that this decline is associated with β-cell dysfunction. Research Design: 40 young (25±3 y) and 53 older (74±7 y) lean non-diabetic subjects underwent a 2 h oral glucose tolerance test (OGTT)...
April 16, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29671912/a-surface-plasmon-resonance-assay-for-characterisation-and-epitope-mapping-of-anti-glp-1-antibodies
#6
Lasse Thomsen, Leonid Gurevich
The incretin hormone glucagon-like peptide-1 (GLP-1) has been subject to substantial pharmaceutical research regarding the treatment of type 2 diabetes mellitus. However, quantification of GLP-1 levels remains complicated due to the low circulation concentration and concurrent existence of numerous metabolites, homologous peptides, and potentially introduced GLP-1 receptor agonists. Surface plasmon resonance (SPR) facilitates real-time monitoring allowing a more detailed characterisation of the interaction compared with conventional enzyme-linked immunosorbent assays (ELISA)...
April 19, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29669745/gpr119-agonism-increases-glucagon-secretion-during-insulin-induced-hypoglycemia
#7
Nina Xiaoyan Li, Stacey Brown, Tim Kowalski, Margaret Wu, Liming Yang, Ge Dai, Aleksandr Petrov, Yuyan Ding, Tamara Dlugos, H Blair Woods, Liangsu Wang, Mark Erion, Robert Sherwin, David E Kelley
Insulin-induced hypoglycemia in diabetes is associated with impaired glucagon secretion. Here we tested whether stimulation of GPR119, a G-protein coupled receptor expressed in pancreatic islet as well as enteroendocrine cells, and previously shown to stimulate insulin and incretin secretion might enhance glucagon secretion during hypoglycemia. In the study, GPR119 agonists were applied to isolated islets or perfused pancreata perfusions to assess insulin and glucagon secretion during hypoglycemia or hyperglycemic conditions...
April 18, 2018: Diabetes
https://www.readbyqxmd.com/read/29669555/the-role-of-dipeptidylpeptidase-4-inhibitors-in-management-of-cardiovascular-disease-in-diabetes-focus-on-linagliptin
#8
REVIEW
Annayya R Aroor, Camila Manrique-Acevedo, Vincent G DeMarco
Multiple population based analyses have demonstrated a high incidence of cardiovascular disease (CVD) and cardiovascular (CV) mortality in subjects with T2DM that reduces life expectancy by as much as 15 years. Importantly, the CV system is particularly sensitive to the metabolic and immune derangements present in obese pre-diabetic and diabetic individuals; consequently, CV dysfunction is often the initial CV derangement to occur and promotes the progression to end organ/tissue damage in T2DM. Specifically, diabetic CVD can manifest as microvascular complications, such as nephropathy, retinopathy, and neuropathy, as well as, macrovascular impairments, including ischemic heart disease, peripheral vascular disease, and cerebrovascular disease...
April 18, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#9
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29664215/the-plasma-bile-acid-alterations-of-type-2-diabetes-correlated-with-insulin-secretion-in-two-step-hyperglycemic-clamp
#10
Shujie Wang, Yuying Deng, Xiaoyan Xie, Jing Ma, Min Xu, Xinjie Zhao, Weiqiong Gu, Jie Hong, Weiqing Wang, Guowang Xu, Guang Ning, Yanyun Gu, Yifei Zhang
BACKGROUND: Bile acids (BAs) conduct crucial signals in human metabolism. Correlations between human plasma BA alterations and insulin secretion defects and type 2 diabetes (T2D) progression have been insufficiently studied. This study was performed to explore the trajectories of human plasma BA alterations and their association with the insulin secretion dynamics during a two-step hyperglycemic clamp. METHODS: Eleven healthy (NGT) and 33 drug-naïve T2D subjects (T2Ds) were enrolled to undertake a two-step hyperglycemic clamp...
April 17, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29656109/bile-acids-are-important-direct-and-indirect-regulators-of-the-secretion-of-appetite-and-metabolism-regulating-hormones-from-the-gut-and-pancreas
#11
Rune E Kuhre, Nicolai J Wewer Albrechtsen, Olav Larsen, Sara L Jepsen, Emilie Balk-Møller, Daniel B Andersen, Carolyn F Deacon, Kristina Schoonjans, Frank Reimann, Fiona M Gribble, Reidar Albrechtsen, Bolette Hartmann, Mette M Rosenkilde, Jens J Holst
OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose...
March 17, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29627373/potential-mechanisms-underlying-differences-in-the-effect-of-incretin-based-antidiabetic-drugs-on-the-risk-of-major-atherosclerotic-ischemic-events
#12
Milton Packer
No abstract text is available yet for this article.
March 24, 2018: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29627317/intestinal-cart-is-a-regulator-of-gip-and-glp-1-secretion-and-expression
#13
L Shcherbina, A Lindqvist, A-H Thorén Fischer, E Ahlqvist, E Zhang, S E Falkmer, E Renström, J Koffert, H Honka, N Wierup
Impaired incretin effect is a culprit in Type 2 Diabetes. Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide controlling pancreatic islet hormone secretion and beta-cell survival. Here we studied the potential expression of CART in enteroendocrine cells and examined the role of CART as a regulator of incretin secretion and expression. CART expression was found in glucose-dependent insulinotropic polypeptide (GIP)-producing K-cells and glucagon-like peptide-1 (GLP-1)-producing L-cells in human duodenum and jejunum and CART levels were increased 60 min after a meal in humans...
April 5, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29623219/management-strategies-for-posttransplant-diabetes-mellitus-after-heart-transplantation-a-review
#14
REVIEW
Matthew G Cehic, Nishant Nundall, Jerry R Greenfield, Peter S Macdonald
Posttransplant diabetes mellitus (PTDM) is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP-) 1 agonists and dipeptidyl peptidase- (DPP-) 4 inhibitors) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of PTDM after heart transplantation...
2018: Journal of Transplantation
https://www.readbyqxmd.com/read/29619563/post-transplantation-diabetes-in-kidney-transplant-recipients-an-update-on-management-and-prevention
#15
Caterina Conte, Antonio Secchi
Post-transplantation diabetes mellitus (PTDM) may severely impact both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. However, PTDM often goes undiagnosed is underestimated or poorly managed. A diagnosis of PTDM should be delayed until the patient is on stable maintenance doses of immunosuppressive drugs, with stable kidney graft function and in the absence of acute infections. Risk factors for PTDM should be assessed during the pre-transplant evaluation period, in order to reduce the likelihood of developing diabetes...
April 4, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29606630/functional-characterization-of-native-high-affinity-gaba-a-receptors-in-human-pancreatic-%C3%AE-cells
#16
Sergiy V Korol, Zhe Jin, Yang Jin, Amol K Bhandage, Anders Tengholm, Nikhil R Gandasi, Sebastian Barg, Daniel Espes, Per-Ola Carlsson, Derek Laver, Bryndis Birnir
In human pancreatic islets, the neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule synthesized by and released from the insulin-secreting β cells. The effective, physiological GABA concentration range within human islets is unknown. Here we use native GABAA receptors in human islet β cells as biological sensors and reveal that 100-1000nM GABA elicit the maximal opening frequency of the single-channels. In saturating GABA, the channels desensitized and stopped working. GABA modulated insulin exocytosis and glucose-stimulated insulin secretion...
March 22, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29606326/dipeptidyl-peptidase-4-inhibitor-vildagliptin-improves-trabecular-bone-mineral-density-and-microstructure-in-obese-insulin-resistant-pre-diabetic-rats
#17
Narattaphol Charoenphandhu, Panan Suntornsaratoon, Piangkwan Sa-Nguanmoo, Pongpan Tanajak, Jarinthorn Teerapornpuntakit, Ratchaneevan Aeimlapa, Nipon Chattipakorn, Siriporn Chattipakorn
OBJECTIVE: Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes...
February 2, 2018: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/29603541/augmentation-of-glucagon-like-peptide-1-receptor-signalling-by-neprilysin-inhibition-potential-implications-for-patients-with-heart-failure
#18
REVIEW
Milton Packer
Augmentation of glucagon-like peptide-1 (GLP-1) receptor signalling is an established approach to the treatment of type 2 diabetes. However, endogenous GLP-1 and long-acting GLP-1 receptor analogues are degraded not only by dipeptidyl peptidase-4, but also by neprilysin. This observation raises the possibilities that endogenous GLP-1 contributes to the clinical effects of neprilysin inhibition and that patients concurrently treated with sacubitril/valsartan and incretin-based drugs may experience important drug-drug interactions...
March 30, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29602791/endogenous-glucose-production-and-hormonal-changes-in-response-to-canagliflozin-and-liraglutide-combination-therapy
#19
Robert Martinez, Hussein Al-Jobori, Ali M Ali, John Adams, Muhammad Abdul-Ghani, Curtis Triplitt, Ralph DeFronzo, Eugenio Cersosimo
The decrement in plasma glucose concentration with SGLT2i is blunted by a rise in endogenous glucose production (EGP). We investigated the ability of incretin treatment to offset the EGP increase. T2DM (n=36) subjects were randomized to: (i) CANAgliflozin (ii) LIRAglutide (iii) CANA/LIRA. EGP was measured with 3-3 H-glucose with/without drug for 360 minutes. In the pre-treatment studies EGP (mg/kg•min) was comparable and decreased (2.2±0.1 to 1.7±0.2) during 300-360 minute period (p<0.01). The decrement in EGP was attenuated with CANA (2...
March 30, 2018: Diabetes
https://www.readbyqxmd.com/read/29600430/targeting-incretin-hormones-and-the-ask-1-pathway-as-therapeutic-options-in-the-treatment-of-non-alcoholic-steatohepatitis
#20
REVIEW
Alexander J Kovalic, Sanjaya K Satapathy, Naga Chalasani
Non-alcoholic fatty liver disease (NAFLD) is currently one of the leading forms of chronic liver disease, and its rising frequency worldwide has reached epidemic proportions. NAFLD, particularly its progressive variant NASH (non-alcoholic steatohepatitis), can lead to advanced fibrosis, cirrhosis, and HCC. The pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex, and as such myriad therapies are under investigation targeting different pathophysiological mechanisms...
March 29, 2018: Hepatology International
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