Glucagon-like peptide 1 (GLP-1)

Müller, Timo; Finan, Brian; Bloom, Stephen R.; D’Alessio, David A.; Drucker, Daniel J.; Flatt, Peter; Fritsche, Andreas; Gribble, Fiona M.; Grill, Harvey J.; Habener, Joel F.; Holst, Jens J.; Langhans, Wolfgang; Meier, Juris J.; Nauck, Michael A.; Pérez-Tilve, Diego; Pocai, Alessandro; Reimann, Frank; Sandoval, Darleen A.; Schwartz, Thue W.; Seeley, Randy J.; Stemmer, Kerstin; Tang-Christensen, Mads; Woods, Stephen C.; DiMarchi, Richard D.; Tschöp, Matthias H.

doi:10.1016/j.molmet.2019.09.010

Cited by 1,065 publications

(1,019 citation statements)

References 968 publications

(1,484 reference statements)

Supporting

Mentioning

861

Contrasting

Unclassified

Order By: Relevance

“…All these actions are transduced by a single GLP-1R located in many organs including the kidney. Among the numerous beneficial effects mediated by GLP-1RA are blood glucose regulation, body weight reduction due to food intake inhibition and reduced gastric motility, cell proliferation stimulation, inflammation and apoptosis reduction, and improved cardiovascular function, neuroprotection and renoprotection [28,29].…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%

“…Impaired proinsulin conversion could explain the mechanism for TCF7L2-associated diminished GLP-1RA efficacy as well as dependent repression of GLP-1R expression on b-cells [32]. Incretin action may also be reduced during hyperglycemia and also in some individuals with prediabetes, diabetes and insulin resistance [28]. Native GLP-1 has a very short half-life (about two minutes) because of rapid degradation by the endogenous enzymes dipeptidyl peptidase (DPP-4) and neutral endopeptidase.…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%

See 1 more Smart Citation

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

Górriz

Soler

Navarro‐González

et al. 2020

JCM

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

show abstract

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

Górriz

Soler

Navarro‐González

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…As one of the most important incretins in the body, GLP-1 can exert hypoglycemic effects through various mechanisms, including promoting insulin secretion and islet beta cell proliferation, inhibiting apoptosis and glucagon secretion, suppressing appetite, and promoting satiety (Bifari et al, 2018). In addition, GLP-1R is widely distributed in a variety of tissues and organs (e.g., islet alpha and beta cells, cardiovascular system, kidney, and gastrointestinal tract) (Muller et al, 2019). GLP-1/GLP-1R signaling regulates the RAS through various signaling mechanisms, which play an essential role in the regulation of target tissue functions.…”

Section: Introductionmentioning

confidence: 99%

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

Yang

Xuan

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and represents a potential therapeutic target for NAFLD. Glucagonlike peptide-1 (GLP-1) signaling has been shown to regulate the RAS within various local tissues. In this study, we aimed to investigate the functional relationship between GLP-1 and the local RAS in the liver during NAFLD. Wild-type and ACE2 knockout mice were used to establish a high-fat-induced NAFLD model. After the mice were treated with liraglutide (a GLP-1 analogue) for 4 weeks, the key RAS component genes were upregulated in the liver of NAFLD mice. Liraglutide treatment regulated the RAS balance, preventing a reduction in fatty acid oxidation gene expression and increasing gluconeogenesis and the expression of inflammation-related genes caused by NAFLD, which were impaired in ACE2 knockout mice. Liraglutide-treated HepG2 cells exhibited activation of the ACE2/Ang1-7/Mas axis, increased fatty acid oxidation gene expression, and decreased inflammation, which could be reversed by A779 and AngII. These results indicate that the local RAS in the liver becomes overactivated in response to NAFLD. Moreover, ACE2 knockout increases the severity of liver steatosis. Liraglutide has a negative and antagonistic effect on the ACE/AngII/AT1R axis, a positive impact on the ACE2/Ang1-7/Mas axis, and is mediated through the PI3K/AKT pathway. This may represent a potential new mechanism by which liraglutide improves NAFLD.

show abstract

“…While insulin treatment remains a major tool in the therapeutic arsenal to restore uncontrolled glycaemia in diabetes, other existing therapies are based on peripheral peptides whose respective receptors are also located in the central nervous system (CNS). Among these peptides, the glucagon-like peptide-1 (GLP-1), which is notably secreted from gut enteroendocrine cells upon nutrient transit, exerts several beneficial actions partly through its ability to enhance glucose-induced insulin release from pancreatic beta-cells (Barrera et al, 2011;Muller et al, 2019). This incretin action has fostered the development of pharmacological agonists of GLP-1 receptor (GLP-1R) for the treatment of T2D and obesity.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, in addition to the incretin effects (Anderson and Trujillo, 2016), GLP-1 promote satiety and lowers body weight (Muller et al, 2019). These actions are believed to be, at least in part, mediated through brain circuits dedicated to the regulation of energy balance (Dodd and Tiganis, 2017;Taouis and Torres-Aleman, 2019).…”

Section: Introductionmentioning

confidence: 99%

Acute changes in systemic glycaemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis

Bakker

Salinas

Imbernón

et al. 2020

Preprint

View full text Add to dashboard Cite

The control of body weight and glucose homeostasis are the bedrock of type 2 diabetes medication. Therapies based on co-administration of glucagon-like peptide-1 (GLP-1) long-acting analogues and insulin are becoming popular in the treatment of T2D. Both insulin and GLP-1 receptors (InsR and GLP1-R, respectively) are expressed in brain regions critically involved in the regulation of energy homeostasis, suggesting a possible cooperative action. However, the mechanisms underlying the synergistic action of insulin and GLP-1R agonists on body weight loss and glucose homeostasis remain largely under-investigated. In this study, we provide evidence that peripheral insulin administration modulates the action of GLP-1R agonists onto fatty acids oxidation. Taking advantage of fluorescently labeled insulin and GLP-1R agonists, we found that glucoprivic condition, either achieved by insulin or by 2-deoxyglucose (2-DG), acts as a permissive signal on the blood-brain barrier (BBB) at circumventricular organs, including the median eminence (ME) and the area postrema (AP), enhancing the passage and action of GLP-1-R agonists. Mechanistically, this phenomenon relied on the release of tanycyctic vascular endothelial growth factor A (VEGF-A) and it was selectively impaired after calorie-rich diet exposure. Finally, we found that in human subjects, low blood glucose also correlates with enhanced blood-to-brain passage of insulin suggesting that changes in glycaemia also affect passage of peptide hormones into the brain in humans. In conclusion, we describe a yet unappreciated mechanism by which acute variations of glycaemia gate the entry and action of circulating energy-related signals in the brain. This phenomenon has physiological and clinical relevance implying that glycemic control is critical to harnessing the full benefit of GLP-1R agonist co-treatment in body weight loss therapy.

show abstract

Glucagon-like peptide 1 (GLP-1)

Cited by 1,065 publications

References 968 publications

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

Liraglutide Attenuates Non-Alcoholic Fatty Liver Disease in Mice by Regulating the Local Renin-Angiotensin System

Acute changes in systemic glycaemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis

Contact Info

Product

Resources

About