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Jens J. Holst - One of the best experts on this subject based on the ideXlab platform.
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Bile acids drive colonic secretion of Glucagon-Like-Peptide 1 and Peptide-YY in rodents
American journal of physiology. Gastrointestinal and liver physiology, 2019Co-Authors: Charlotte B. Christiansen, Nicolai J. Wewer Albrechtsen, Rune E. Kuhre, Samuel A.j. Trammell, Kristina Schoonjans, Reidar Albrechtsen, Matthew P. Gillum, Jens J. HolstAbstract:By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic Glucagon-Like-Peptide 1 and Peptide-YY secretion. The study provides con...
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glucagon like Peptide 1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy
American Journal of Physiology-endocrinology and Metabolism, 2016Co-Authors: Ali Asmar, Sten Madsbad, Lene Simonsen, Meena Asmar, Erik Frandsen, Cedric Moro, Charlotte Mehlin Sorensen, Thomas E N Jonassen, Jens J. Holst, Jens BulowAbstract:During acute administration of native Glucagon-Like Peptide-1 (GLP-1), we previously demonstrated central hemodynamic effects in healthy males, whereas renal hemodynamics, despite renal uptake of G...
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secretion of glucagon like Peptide 1 in patients with type 2 diabetes mellitus systematic review and meta analyses of clinical studies
Diabetologia, 2013Co-Authors: Salvatore Calanna, Tina Vilsbøll, Jens J. Holst, Mikkel B Christensen, Blandine Laferrere, Lise Lotte Gluud, Filip K. KnopAbstract:Aims/hypothesis We carried out a systematic review of clinical studies investigating Glucagon-Like Peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test.
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glucagon like Peptide 1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia
Journal of Cerebral Blood Flow and Metabolism, 2012Co-Authors: Jens J. Holst, Niels Moller, Michael Gejl, Laerke Egefjord, Susanne Lerche, Kim Vang, Bo Martin Bibby, A Mengel, Jorgen RungbyAbstract:Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that Glucagon-Like Peptide-1 (GLP-1) may be neuroprotective in models of AD and stroke: Although the mechanism is unclear, glucose homeostasis appears to be important. We conducted a randomized, double-blinded, placebo-controlled crossover study in nine healthy males. Positron emission tomography was used to determine the effect of GLP-1 on cerebral glucose transport and metabolism during a hyperglycemic clamp with 18fluoro-deoxy-glucose as tracer. Glucagon-Like Peptide-1 lowered brain glucose (P=0.023) in all regions. The cerebral metabolic rate for glucose was increased everywhere (P=0.039) but not to the same extent in all regions (P=0.022). The unidirectional glucose transfer across the blood–brain barrier remained unchanged (P=0.099) in all regions, while the unidirectional clearance and the phosphorylation rate increased (P=0.013 and 0.017), leading to increased net clearance of the glucose tracer (P=0.006). We show that GLP-1 plays a role in a regulatory mechanism involved in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia.
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the effect of glucagon like Peptide 1 on cardiovascular risk
Nature Reviews Cardiology, 2012Co-Authors: Jacob Sivertsen, Jaya B Rosenmeier, Jens J. Holst, Tina VilsbøllAbstract:Glucagon-Like Peptide 1 (GLP)-based therapies reduce blood glucose levels in patients with type 2 diabetes mellitus. Interestingly, GLP 1 receptor agonists can also have beneficial effects on cardiovascular risk. Dr. Sivertsen and colleagues provide an overview of the cardiovascular mechanisms targeted by GLP 1-based therapies and discuss clinical data for long-term management of cardiovascular risk in patients treated with these agents. Glucagon-Like Peptide 1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally, as opposed to intravenously, and it retains its insulinotropic activity in patients with type 2 diabetes mellitus. GLP-1-based therapies, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4, an enzyme that degrades endogenous GLP-1, have established effectiveness in lowering glucose levels and are routinely used to treat patients with type 2 diabetes. These agents regulate glucose metabolism through multiple mechanisms and have several effects on cardiovascular parameters. These effects, possibly independent of the glucose-lowering activity, include changes in blood pressure, endothelial function, body weight, cardiac metabolism, lipid metabolism, left ventricular function, atherosclerosis, and the response to ischemia–reperfusion injury. Thus, GLP-1-based therapies could potentially target both diabetes and cardiovascular disease. This Review highlights the mechanisms targeted by GLP-1-based therapies, and emphasizes current developments in incretin research that are relevant to cardiovascular risk and disease, as well as treatment with GLP-1 receptor agonists.
Daniel J Drucker - One of the best experts on this subject based on the ideXlab platform.
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glucagon like Peptide 1 glp 1
Molecular metabolism, 2019Co-Authors: Timo D Muller, Fiona M Gribble, David A Dalessio, Daniel J Drucker, Brian Finan, Stephen R Bloom, Peter R Flatt, Andreas Fritsche, Harvey J Grill, Joel F HabenerAbstract:Abstract Background The Glucagon-Like Peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. Scope of review In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. Major conclusions Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders
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cardiovascular actions and clinical outcomes with glucagon like Peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors
Circulation, 2017Co-Authors: Michael A. Nauck, Juris J Meier, Matthew A Cavender, Mirna Abd El Aziz, Daniel J DruckerAbstract:Potentiation of Glucagon-Like Peptide-1 (GLP-1) action through selective GLP-1 receptor (GLP-1R) agonism or by prevention of enzymatic degradation by inhibition of dipeptidyl peptidase-4 (DPP-4) pr...
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the cardiovascular biology of glucagon like Peptide 1
Cell Metabolism, 2016Co-Authors: Daniel J DruckerAbstract:Glucagon-Like Peptide-1, produced predominantly in enteroendocrine cells, controls glucose metabolism and energy homeostasis through regulation of islet hormone secretion, gastrointestinal motility, and food intake, enabling development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. GLP-1 also acts on the immune system to suppress inflammation, and GLP-1R signaling in multiple tissues impacts cardiovascular function in health and disease. Here we review how GLP-1 and clinically approved GLP-1R agonists engage mechanisms that influence the risk of developing cardiovascular disease. We discuss how GLP-1R agonists modify inflammation, cardiovascular physiology, and pathophysiology in normal and diabetic animals through direct and indirect mechanisms and review human studies illustrating mechanisms linking GLP-1R signaling to modification of the cardiovascular complications of diabetes. The risks and benefits of GLP-1R agonists are updated in light of recent data suggesting that GLP-1R agonists favorably modify outcomes in diabetic subjects at high risk for cardiovascular events.
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a glucagon like Peptide 1 analog reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity
Circulation, 2013Co-Authors: Mohammad Hossein Noyanashraf, Daniel J Drucker, Eric A Shikatani, Irmgard Schuiki, Ilya Mukovozov, Allen Volchuk, Lisa A Robinson, Filio Billia, Mansoor HusainAbstract:Background—Cardiac consequences of obesity include inflammation, hypertrophy, and compromised energy metabolism. Glucagon-Like Peptide-1 is an incretin hormone capable of cytoprotective actions that reduces inflammation and endoplasmic reticulum stress in other tissues. Here we examine the cardiac effects of the Glucagon-Like Peptide-1 analog liraglutide in a model of obesity, independent of changes in body weight. Methods and Results—C57Bl6 mice were placed on a 45% high-fat diet (HFD) or a regular chow diet. Mice on HFD developed 46±2% and 60±2% greater body weight relative to regular chow diet–fed mice at 16 and 32 weeks, respectively (both P<0.0001), manifesting impaired glucose tolerance, insulin resistance, and cardiac ceramide accumulation by 16 weeks. One-week treatment with liraglutide (30 µg/kg twice daily) did not reduce body weight, but reversed insulin resistance, cardiac tumor necrosis factor-α expression, nuclear factor kappa B translocation, obesity-induced perturbations in cardiac endothe...
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the glucagon like Peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice
Diabetologia, 2010Co-Authors: Joanne Hsieh, Daniel J Drucker, Christine Longuet, Christopher Baker, B Qin, Lisa Federico, Khosrow AdeliAbstract:Aims/hypothesis Glucagon-Like Peptide 1 (GLP-1) receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors attenuate postprandial lipaemia through mechanisms that remain unclear. As dyslipidaemia is a contributing risk factor for cardiovascular disease in type 2 diabetes, we examined the mechanisms linking pharmacological and physiological regulation of GLP-1 action to control of postprandial lipid metabolism.
Carolyn F. Deacon - One of the best experts on this subject based on the ideXlab platform.
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Measurement of the incretin hormones: Glucagon-Like Peptide-1 and glucose-dependent insulinotropic Peptide.
Journal of diabetes and its complications, 2014Co-Authors: Rune E. Kuhre, Nicolai J. Wewer Albrechtsen, Bolette Hartmann, Carolyn F. DeaconAbstract:The two incretin hormones, Glucagon-Like Peptide 1 (GLP-1) and glucose-dependent insulinotropic Peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma concentrations of GLP-1 and GIP is often an important endpoint in both clinical and preclinical studies and, therefore, accurate measurement of these hormones is important. Here, we provide an overview of current approaches for the measurement of the incretin hormones, with particular focus on immunological methods.
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glucagon like Peptide 1 glucose homeostasis and diabetes
Trends in Molecular Medicine, 2008Co-Authors: Carolyn F. Deacon, Tina Vilsbøll, Thure Krarup, Sten MadsbadAbstract:Incretins, enhancers of insulin secretion, are essential for glucose tolerance, and a reduction in their function might contribute to poor β-cell function in patients with type-2 diabetes mellitus. However, at supraphysiological doses, the incretin Glucagon-Like Peptide-1 (GLP-1) protects pancreatic β cells, and inhibits glucagon secretion, gastric emptying and food intake, leading to weight loss. GLP-1 mimetics, which are stable-Peptide-based activators of the GLP-1 receptor, and incretin enhancers, which inhibit the incretin-degrading enzyme dipeptidyl peptidase-4, have emerged as therapies for type-2 diabetes and have recently reached the market. The pathophysiological basis the clinical use of these therapeutics is reviewed here.
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glucagon like Peptide 1 and inhibitors of dipeptidyl peptidase iv in the treatment of type 2 diabetes mellitus
Current Opinion in Pharmacology, 2004Co-Authors: Jens J. Holst, Carolyn F. DeaconAbstract:Proof-of-concept for the efficacy of a Glucagon-Like Peptide 1 (GLP-1)-based therapy of patients with type 2 diabetes was provided in 2002 by means of prolonged continuous subcutaneous infusion of native GLP-1. Since then, several long-acting analogues of GLP-1, as well as inhibitors of dipeptidyl peptidase IV, the enzyme that rapidly inactivates endogenous GLP-1, have demonstrated efficacy in long term clinical trials.
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glucagon like Peptide 1 undergoes differential tissue specific metabolism in the anesthetized pig
American Journal of Physiology-endocrinology and Metabolism, 1996Co-Authors: Carolyn F. Deacon, L Pridal, L Klarskov, M OlesenAbstract:Glucagon-Like Peptide 1 (GLP-1) metabolism was studied in halothane-anesthetized pigs (n = 7) using processing-independent (PI) and COOH-terminal (C) radioimmunoassays (RIA) and an enzyme-linked im...
Tina Vilsbøll - One of the best experts on this subject based on the ideXlab platform.
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glucagon like Peptide 1 in health and disease
Nature Reviews Endocrinology, 2018Co-Authors: Andreas Andersen, Filip K. Knop, Asger Lund, Tina VilsbøllAbstract:In healthy individuals, the incretin hormone Glucagon-Like Peptide 1 (GLP1) potentiates insulin release and suppresses glucagon secretion in response to the ingestion of nutrients. GLP1 also delays gastric emptying and increases satiety. In patients with type 2 diabetes mellitus (T2DM), supraphysiological doses of GLP1 normalize the endogenous insulin response during a hyperglycaemic clamp. Owing to the short plasma half-life of native GLP1, several GLP1 receptor agonists (GLP1RAs) with longer half-lives have been developed for the treatment of T2DM. These compounds vary in chemical structure, pharmacokinetics and size, which results in different clinical effects on hyperglycaemia and body weight loss; these variations might also explain the difference in cardiovascular effect observed in large-scale cardiovascular outcome trials, in which certain GLP1RAs were shown to have a positive effect on cardiovascular outcomes. Owing to their metabolic effects, GLP1RAs are also considered for the treatment of several other lifestyle-induced conditions, such as obesity, prediabetes and liver disease. This Review provides insights into the physiology of GLP1 and its involvement in the pathophysiology of T2DM and an overview of the currently available and emerging GLP1RAs. Furthermore, we review the results from the currently available large-scale cardiovascular outcome trials and the use of GLP1RAs for other indications.
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Unprecedented high insulin secretion in a healthy human subject after intravenous Glucagon-Like Peptide-1: a case report
BMC research notes, 2014Co-Authors: Filip K. Knop, Asger Lund, Sten Madsbad, Thure Krarup, Tina VilsbøllAbstract:Background The gut-derived incretin hormones, glucose-dependent insulinotropic polyPeptide and Glucagon-Like Peptide-1, are released in response to ingestion of nutrients. Both hormones are highly insulinotropic in strictly glucose-dependent fashions and Glucagon-Like Peptide-1 is often referred to as one of the most insulinotropic substances known.
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secretion of glucagon like Peptide 1 in patients with type 2 diabetes mellitus systematic review and meta analyses of clinical studies
Diabetologia, 2013Co-Authors: Salvatore Calanna, Tina Vilsbøll, Jens J. Holst, Mikkel B Christensen, Blandine Laferrere, Lise Lotte Gluud, Filip K. KnopAbstract:Aims/hypothesis We carried out a systematic review of clinical studies investigating Glucagon-Like Peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test.
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the effect of glucagon like Peptide 1 on cardiovascular risk
Nature Reviews Cardiology, 2012Co-Authors: Jacob Sivertsen, Jaya B Rosenmeier, Jens J. Holst, Tina VilsbøllAbstract:Glucagon-Like Peptide 1 (GLP)-based therapies reduce blood glucose levels in patients with type 2 diabetes mellitus. Interestingly, GLP 1 receptor agonists can also have beneficial effects on cardiovascular risk. Dr. Sivertsen and colleagues provide an overview of the cardiovascular mechanisms targeted by GLP 1-based therapies and discuss clinical data for long-term management of cardiovascular risk in patients treated with these agents. Glucagon-Like Peptide 1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally, as opposed to intravenously, and it retains its insulinotropic activity in patients with type 2 diabetes mellitus. GLP-1-based therapies, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4, an enzyme that degrades endogenous GLP-1, have established effectiveness in lowering glucose levels and are routinely used to treat patients with type 2 diabetes. These agents regulate glucose metabolism through multiple mechanisms and have several effects on cardiovascular parameters. These effects, possibly independent of the glucose-lowering activity, include changes in blood pressure, endothelial function, body weight, cardiac metabolism, lipid metabolism, left ventricular function, atherosclerosis, and the response to ischemia–reperfusion injury. Thus, GLP-1-based therapies could potentially target both diabetes and cardiovascular disease. This Review highlights the mechanisms targeted by GLP-1-based therapies, and emphasizes current developments in incretin research that are relevant to cardiovascular risk and disease, as well as treatment with GLP-1 receptor agonists.
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the effect of glucagon like Peptide 1 on cardiovascular risk
Nature Reviews Cardiology, 2012Co-Authors: Jacob Sivertsen, Jaya B Rosenmeier, Jens J. Holst, Tina VilsbøllAbstract:Glucagon-Like Peptide 1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally, as opposed to intravenously, and it retains its insulinotropic activity in patients with type 2 diabetes mellitus. GLP-1-based therapies, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4, an enzyme that degrades endogenous GLP-1, have established effectiveness in lowering glucose levels and are routinely used to treat patients with type 2 diabetes. These agents regulate glucose metabolism through multiple mechanisms and have several effects on cardiovascular parameters. These effects, possibly independent of the glucose-lowering activity, include changes in blood pressure, endothelial function, body weight, cardiac metabolism, lipid metabolism, left ventricular function, atherosclerosis, and the response to ischemia-reperfusion injury. Thus, GLP-1-based therapies could potentially target both diabetes and cardiovascular disease. This Review highlights the mechanisms targeted by GLP-1-based therapies, and emphasizes current developments in incretin research that are relevant to cardiovascular risk and disease, as well as treatment with GLP-1 receptor agonists.
Steve Bloom - One of the best experts on this subject based on the ideXlab platform.
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Theme Gastrointestinal Satiety Signals III. Glucagon-Like Peptide 1, oxyntomodulin, Peptide YY, and pancreatic polyPeptide
2016Co-Authors: Sarah Stanley, Katie Wynne, Steve Bloom, Steve Bloom GastrointestinalAbstract:satiety signals. III. Glucagon-Like Peptide 1, oxyntomodulin, peptid
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Gastrointestinal satiety signals. III. Glucagon-Like Peptide 1, oxyntomodulin, Peptide YY, and pancreatic polyPeptide
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2004Co-Authors: Sarah Stanley, Katie Wynne, Steve BloomAbstract:Many Peptides are synthesized and released from the gastrointestinal tract and pancreas, including pancreatic polyPeptide (PP) and the products of the gastrointestinal L cells, Glucagon-Like Peptide 1 (GLP-1), oxyntomodulin, and Peptide YY (PYY). Whereas their roles in regulation of gastrointestinal function have been known for some time, it is now evident that they also influence eating behavior. This review considers the anorectic Peptides PYY, PP, GLP-1, and oxyntomodulin, which decrease appetite and promote satiety in both animal models and humans.