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Incretins

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https://www.readbyqxmd.com/read/28336086/incretin-hormones-regulate-microglia-oxidative-stress-survival-and-expression-of-trophic-factors
#1
Lindsay Joy Spielman, Deanna Lynn Gibson, Andis Klegeris
The incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are primarily known for their metabolic function in the periphery. GLP-1 and GIP are secreted by intestinal endocrine cells in response to ingested nutrients. Both GLP-1 and GIP stimulate the production and release of insulin from pancreatic β cells as well as exhibit several growth-regulating effects on peripheral tissues. GLP-1 and GIP are also present in the brain, where they provide modulatory and anti-apoptotic signals to neurons...
March 8, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28324023/long-chain-free-fatty-acid-receptor-gpr120-mediates-oil-induced-gip-secretion-through-cck-in-male-mice
#2
Akiko Sankoda, Norio Harada, Kanako Iwasaki, Shunsuke Yamane, Yuki Murata, Kimitaka Shibue, Yotsapon Thewjitcharoen, Kazuyo Suzuki, Takanari Harada, Yoshinori Kanemaru, Satoko Shimazu-Kuwahara, Akira Hirasawa, Nobuya Inagaki
Free fatty acid receptors GPR120 and GPR40 are involved in the secretion of gut hormones. GPR120 and GPR40 are expressed in enteroendocrine K-cells and their activation induces the secretion of the incretin glucose-dependent insulinotropic polypeptide (GIP). However, the role of these receptors in fat-induced GIP secretion in vivo and the associated mechanisms are unclear. In this study, we investigated corn oil-induced GIP secretion in GPR120-knockout (GPR120-/-) and GPR40-knockout (GPR40-/-) mice. Oil-induced GIP secretion was reduced by 50% and 80% in GPR120-/- and GPR40-/- mice compared to that in wild-type (WT) mice, respectively...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323942/incretin-therapies-do-not-expand-%C3%AE-cell-mass-or-alter-pancreatic-histology-in-young-male-mice
#3
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, considerable disagreement exists on whether incretins actually increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
March 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28321312/preserved-glucagon-like-peptide-1-responses-to-oral-glucose-but-reduced-incretin-effect-insulin-secretion-and-sensitivity-in-young-asians-with-type-2-diabetes-mellitus
#4
Toh Peng Yeow, Giovanni Pacini, Andrea Tura, Chee Peng Hor, Shueh Lin Lim, Florence Hui Sieng Tan, Chin Voon Tong, Janet Yeow Hua Hong, Fuziah Md Zain, Jens Juul Holst, Wan Nazaimoon Wan Mohamud
OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index...
2017: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#5
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28298900/the-impact-of-bariatric-surgery-on-type-2-diabetes-mellitus-and-the-management-of-hypoglycemic-events
#6
REVIEW
Mahmoud Attia Mohamed Kassem, Michael Andrew Durda, Nicoleta Stoicea, Omer Cavus, Levent Sahin, Barbara Rogers
Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28294170/exploring-inter-organ-crosstalk-to-uncover-mechanisms-that-regulate-%C3%AE-cell-function-and-mass
#7
REVIEW
J Shirakawa, D F De Jesus, R N Kulkarni
Impaired β-cell function and insufficient β-cell mass compensation are twin pathogenic features that underlie type 2 diabetes (T2D). Current therapeutic strategies continue to evolve to improve treatment outcomes in different ethnic populations and include approaches to counter insulin resistance and improve β-cell function. Although the effects of insulin secretion on metabolic organs such as liver, skeletal muscle and adipose is directly relevant for improving glucose uptake and reduce hyperglycemia, the ability of pancreatic β-cells to crosstalk with multiple non-metabolic tissues is providing novel insights into potential opportunities for improving β-cell function and/or mass that could have beneficial effects in patients with diabetes...
March 15, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28285800/perspectives-on-cardiovascular-effects-of-incretin-based-drugs-from-bedside-to-bench-return-trip
#8
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28284167/albiglutide-for-the-treatment-of-type-2-diabetes-mellitus-an-integrated-safety-analysis-of-the-harmony-phase-3-trials
#9
Bo Ahrén, Molly C Carr, Karen Murphy, Christopher Perkins, Marc Rendell, Jason Mallory, Timothy Wilson, Susan Johnson
AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM. METHODS: Integrated safety analysis included seven phase-3 T2DM studies of albiglutide compared with placebo and/or active comparators (a dipeptidyl peptidase-4 inhibitor, GLP-1 RA, insulin, sulphonylurea, and thiazolidinedione)...
February 20, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28275047/the-new-biology-and-pharmacology-of-glucagon
#10
REVIEW
T D Müller, B Finan, C Clemmensen, R D DiMarchi, M H Tschöp
In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28274625/apd668-a-g-protein-coupled-receptor-119-agonist-improves-fat-tolerance-and-attenuates-fatty-liver-in-high-trans-fat-diet-induced-steatohepatitis-model-in-c57bl-6-mice
#11
Umakant Ashok Bahirat, Rekha Raghuveer Shenoy, Rajan Naresh Goel, Kumar V S Nemmani
G-protein coupled receptor 119 (GPR119) receptor is a rhodopsin-like, class A Gαs-coupled receptor, predominantly expressed in pancreatic islet cells and intestinal entero-endocrine cells. GPR119 has been emerged as a novel therapeutic target for the treatment of dyslipidemia in type 2 diabetes. In this study, we investigated the effect of APD668, a GPR119 agonist alone and in combination with linagliptin, a DPPIV inhibitor on oral fat tolerance test. Our findings demonstrate that APD668, a GPR119 agonist inhibits the intestinal triglyceride absorption after acute fat load in mice...
March 6, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28270062/antidiabetic-drugs-and-the-kidney
#12
Moses Elisaf, Eleftheria Tzavela, Nikolaos Karanatsis, Vasilis Tsimichodimos
OBJECTIVE: Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism...
March 6, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28258126/effects-of-meal-and-incretins-in-the-regulation-of-splanchnic-blood-flow
#13
Jukka Koffert, Henri Honka, Jarmo Teuho, Saila Kauhanen, Saija Hurme, Riitta Parkkola, Vesa Oikonen, Andrea Mari, Andreas Lindqvist, Nils Wierup, Leif Groop, Pirjo Nuutila
OBJECTIVE: Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. DESIGN: Non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation...
March 3, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28254842/%C3%AE-cell-inactivation-of-gpr119-unmasks-incretin-dependence-of-gpr119-mediated-glucoregulation
#14
Brandon L Panaro, Grace B Flock, Jonathan E Campbell, Jacqueline L Beaudry, Xiemin Cao, Daniel J Drucker
GPR119 was originally identified as an orphan β-cell receptor however subsequent studies demonstrated that GPR119 also regulates β-cell function indirectly through incretin hormone secretion. We assessed the importance of GPR119 for β-cell function in Gpr119(-/-) mice and in newly generated Gpr119(βcell-/-) mice. Gpr119(-/-) mice displayed normal body weight and glucose tolerance on a regular chow diet. After high fat feeding, Gpr119(-/-) mice exhibited reduced fat mass, decreased levels of circulating adipokines, improved insulin sensitivity and better glucose tolerance...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28250160/glucose-dependent-insulinotropic-polypeptide-receptor-deficiency-leads-to-impaired-bone-marrow-hematopoiesis
#15
Fernanda Dana Mantelmacher, Sigal Fishman, Keren Cohen, Metsada Pasmanik Chor, Yuichiro Yamada, Isabel Zvibel, Chen Varol
The bone marrow (BM) contains controlled specialized microenvironments, or niches, that regulate the quiescence, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPC). The glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that mediates postprandial insulin secretion and has anabolic effects on adipose tissue. Previous studies demonstrated altered bone microarchitecture in mice deficient for GIP receptor (Gipr(-/-) ), as well as the expression of high-affinity GIP receptor by distinct cells constructing the BM HSPC niche...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28249585/incretin-based-agents-in-type-2-diabetic-patients-at-cardiovascular-risk-compare-the-effect-of-glp-1-agonists-and-dpp-4-inhibitors-on-cardiovascular-and-pancreatic-outcomes
#16
Zeqing Zhang, Xi Chen, Puhan Lu, Jianhua Zhang, Yongping Xu, Wentao He, Mengni Li, Shujun Zhang, Jing Jia, Shiying Shao, Junhui Xie, Yan Yang, Xuefeng Yu
BACKGROUND: Incretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk. METHODS: Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia...
March 1, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28242789/tm6sf2-rs58542926-variant-affects-postprandial-lipoprotein-metabolism-and-glucose-homeostasis-in-nafld-a-clue-to-the-opposite-impact-of-tm6sf2-variant-on-liver-and-cardio-metabolic-disease
#17
Giovanni Musso, Ugo Cipolla, Maurizio Cassader, Silvia Pinach, Francesca Saba, Franco De Michieli, Elena Paschetta, Daria Bongiovanni, Luciana Framarin, Nicola Leone, Mara Berrutti, Floriano Rosina, Stefania Corvisieri, Federica Molinaro, Antonio Sircana, Roberto Gambino
Mechanisms underlying the opposite effects of TM6SF2 rs58542926 C>T polymorphism on liver injury and cardio-metabolic risk in NAFLD are unclear. We assessed the impact of this polymorphism on postprandial lipoprotein metabolism, glucose homeostasis, and nutrient oxidation in NAFLD. Sixty nonobese, nondiabetic, normolipidemic biopsy-proven NAFLD patients and 60 matched controls genotyped for TM6SF2 C>T polymorphism underwent: indirect calorimetry, an oral fat tolerance test with measurement of plasma lipoprotein subfractions, adipokines, incretin GIP, and an OGTT with Minimal Model analysis of glucose homeostasis...
February 27, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28242256/gastric-bypass-in-the-pig-increases-gip-levels-and-decreases-active-glp-1-levels
#18
Andreas Lindqvist, Mikael Ekelund, Stefan Pierzynowski, Leif Groop, Jan Hedenbro, Nils Wierup
Gastric bypass surgery results in remission of type 2 diabetes in the majority of patients. The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been implicated in the observed remission. Most knowledge so far has been generated in obese subjects. To isolate the surgical effects of gastric bypass on metabolism and hormone responses from the confounding influence of obesity, T2D, or food intake, we performed gastric bypass in lean pigs, using sham-operated and pair-fed pigs as controls...
February 24, 2017: Peptides
https://www.readbyqxmd.com/read/28237410/glucagon-like-peptide-1-glp-1-increases-in-plasma-and-colon-tissue-prior-to-estrus-and-circulating-levels-change-with-increasing-age-in-reproductively-competent-wistar-rats
#19
Michelle L Johnson, M Jill Saffrey, Victoria J Taylor
There is a well-documented association between cyclic changes to food intake and the changing ovarian hormone levels of the reproductive cycle in female mammals. Limited research on appetite-controlling gastrointestinal peptides has taken place in females, simply because regular reproductive changes in steroid hormones present additional experimental factors to account for. This study focussed directly on the roles that gastrointestinal-secreted peptides may have in these reported, naturally occurring, changes to food intake during the rodent estrous cycle and aimed to determine whether peripheral changes occurred in the anorexigenic (appetite-reducing) hormones peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1) in female Wistar rats (32-44 weeks of age)...
February 22, 2017: Peptides
https://www.readbyqxmd.com/read/28235848/patients-with-long-qt-syndrome-due-to-impaired-herg-encoded-kv11-1-potassium-channel-have-exaggerated-endocrine-pancreatic-and-incretin-function-associated-with-reactive-hypoglycemia
#20
Louise Hyltén-Cavallius, Eva W Iepsen, Nicolai J Wewer Albrechtsen, Mathilde Svendstrup, Anniek F Lubberding, Bolette Hartmann, Thomas Jespersen, Allan Linneberg, Michael Christiansen, Henrik Vestergaard, Oluf Pedersen, Jens J Holst, Jørgen K Kanters, Torben Hansen, Signe S Torekov
Background -Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long QT syndrome (LQT2) due to prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), respectively. These hormones are crucial for glucose regulation and LQTS may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and β cell- and decreased α cell function and thus lower glucose levels...
February 24, 2017: Circulation
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