ArticleAmerican journal of physiology. Endocrinology and metabolism2010
Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Initial evidence that GLP-1 receptor blockade fails to suppress postprandial satiety or promote food intake in humans.Appetite · 2014Trial
- Exendin-4 improves neurodevelopmental outcome after neonatal germinal matrix hemorrhage.Cell death & disease · 2026Article
- GLP-1R biased cAMP agonism maintains glycemic control with reduced malaise and emesis in preclinical mammalian models.Diabetes, obesity & metabolism · 2026Article
- Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.Comprehensive Physiology · 2025Review
- Aged garlic extract preserves beta-cell functioning via modulation of nuclear factor kappa-B (NF-κB)/Toll-like receptor (TLR)-4 and sarco endoplasmic reticulum calcium ATPase (SERCA)/CaDiabetology & metabolic syndrome · 2024Article
- Glucagon-like peptide-1 receptor agonists for treatment of diabetes and obesity: advantage of oral delivery.Frontiers in drug delivery · 2024Article
- Review
- Macronutrient intake: Hormonal controls, pathological states, and methodological considerations.Appetite · 2023Review
- The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 does not affect food intake in rats.Pharmacology, biochemistry, and behavior · 2022Article
- Bolus Injection of Liraglutide Raises Plasma Glucose in Normal Rats by Activating Glucagon-like Peptide 1 Receptor in the Brain.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Glucose-sensing glucagon-like peptide-1 receptor neurons in the dorsomedial hypothalamus regulate glucose metabolism.Science advances · 2022Article
- GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition.Circulation research · 2022Article
- Glucagon-like peptide-1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?British journal of pharmacology · 2022Review
- The role of glia in the physiology and pharmacology of glucagon-like peptide-1: implications for obesity, diabetes, neurodegeneration and glaucoma.British journal of pharmacology · 2022Review
- Type 2 Diabetes Mellitus (T2DM) and Carbohydrate Metabolism in Relation to T2DM from Endocrinology, Neurophysiology, Molecular Biology, and Biochemistry Perspectives.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is).Diabetes, metabolic syndrome and obesity : targets and therapy · 2021 · on this mapReview
- GLP-1 Receptor Signaling Differentially Modifies the Outcomes of Sterile vs Viral Pulmonary Inflammation in Male Mice.Endocrinology · 2020Article
- Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress.Nutrients · 2020Review
- A second-generation glucagon-like peptide-1 receptor agonist mitigates vomiting and anorexia while retaining glucoregulatory potency in lean diabetic and emetic mammalian models.Diabetes, obesity & metabolism · 2020Article
- Rapid hepatic metabolism blunts the endocrine action of portally infused GLP-1 in male rats.American journal of physiology. Endocrinology and metabolism · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Exendin-4 (Ex-4), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), shares many of the actions of GLP-1 on pancreatic islets, the central nervous system (CNS), and the gastrointestinal tract that mediates glucose homeostasis and food intake. Because Ex-4 has a much longer plasma half-life than GLP-1, it is an effective drug for reducing blood glucose levels in patients with type 2 diabetes mellitus (T2DM). Here, we report that acute administration of Ex-4, in relatively high doses, into either the peripheral circulation or the CNS, paradoxically increased blood glucose levels in rats. This effect was independent of the insulinotropic and hypothalamic-pituitary-adrenal activating actions of Ex-4 and could be blocked by a GLP-1R antagonist. Comparable doses of GLP-1 did not induce hyperglycemia, even when protected from rapid metabolism by a dipeptidyl peptidase IV inhibitor. Acute hyperglycemia induced by Ex-4 was blocked by hexamethonium, guanethidine, and adrenal medullectomy, indicating that this effect was mediated by sympathetic nervous system (SNS) activation. The potency of Ex-4 to elevate blood glucose waned with chronic administration such that after 6 days the familiar actions of Ex-4 to improve glucose tolerance were evident. These findings indicate that, in rats, high doses of Ex-4 activate a SNS response that can overcome the expected benefits of this peptide on glucose metabolism and actually raise blood glucose. These results have important implications for the design and interpretation of studies using Ex-4 in rats. Moreover, since there are many similarities in the response of the GLP-1R system across mammalian species, it is important to consider whether there is acute activation of the SNS by Ex-4 in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.