ArticleDiabetologia2008
Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.
- Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled TrialsJournal of clinical research in pediatric endocrinology · 2024Pooled it
- Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.Diabetes & metabolism journal · 2019Trial
- Efficacy and safety of sitagliptin added to insulin in Japanese patients with type 2 diabetes: the EDIT randomized trial.PloS one · 2015Trial
- Trial
- Intra-Islet Paracrine Regulation of Glucagon Secretion During Hypoglycemia, Euglycemia, and Hyperglycemia.Annals of the New York Academy of Sciences · 2026Review
- Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications.Cardiovascular drugs and therapy · 2026Review
- Incretin hormones and obesity.The Journal of physiology · 2025Review
- Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data.Current obesity reports · 2025Review
- GLP-1-based therapies for type 2 diabetes: from single, dual and triple agonists to endogenous GLP-1 production and L-cell differentiation.Diabetology & metabolic syndrome · 2025Review
- Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes.World journal of diabetes · 2025Article
- GLP-1R in diabetes mellitus: from basic discovery to therapeutics development.Frontiers in pharmacology · 2025Review
- New Insights into Chronic Pancreatitis: Potential Mechanisms Related to Probiotics.Microorganisms · 2024Review
- Evaluating glucose-dependent insulinotropic polypeptide and glucagon as key regulators of insulin secretion in the pancreatic islet.American journal of physiology. Endocrinology and metabolism · 2024Review
- GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells.Peptides · 2024Article
- GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion.Diabetologia · 2024Article
- Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists.Frontiers in endocrinology · 2024Review
- The intestine as an endocrine organ and the role of gut hormones in metabolic regulation.Nature reviews. Gastroenterology & hepatology · 2023Review
- Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets.American journal of physiology. Endocrinology and metabolism · 2023Review
- Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes.Journal of diabetes investigation · 2023Article
- Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes.Frontiers in pharmacology · 2023Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe glucose-lowering effect of glucagon-like peptide-1 (GLP-1) is based not only upon its potent insulinotropic actions but also on its ability to restrain glucagon secretion. Surprisingly, the closely related glucose-dependent insulinotropic peptide (GIP) stimulates glucagon release. We examined whether the islet hormone somatostatin, which strongly inhibits glucagon secretion, is involved in this divergent behaviour.
methodsAt 1.5 mmol/l glucose and therefore minimal insulin secretion, the glucagon, insulin and somatostatin responses to 20 mmol/l glucose, GLP-1, GIP and somatostatin were studied in the presence of a high-affinity monoclonal somatostatin antibody and of a highly specific somatostatin receptor subtype 2 (SSTR2) antagonist (PRL-2903) in the isolated perfused rat pancreas.
resultsIn control experiments, GLP-1 at 1 and 10 nmol/l reduced glucagon secretion significantly to 59.0 +/- 6.3% (p < 0.004; n = 5; SSTR2 series; each vs pre-infusion level) and to 48.0 +/- 2.6% (p < 0.001; n = 6; somatostatin antibody series) respectively. During somatostatin antibody administration, GLP-1 still inhibited glucagon secretion significantly, but the effect was less pronounced than in control experiments (p < 0.018). Co-infusion of the SSTR2 antagonist completely abolished the GLP-1-induced suppression of glucagon secretion. In contrast, neither the GIP-induced stimulation of glucagon release nor its inhibition by 20 mmol/l glucose was altered by somatostatin antibody or SSTR2 antagonist administration. CONCLUSIONS/
interpretationWe conclude that GLP-1 is capable of inhibiting glucagon secretion even in the absence of secretory products from the beta cell. It is highly likely that this is mediated via somatostatin interacting with SSTR2 on rat alpha cells. In contrast, GIP and glucose seem to influence the alpha cell independently of somatostatin secretion.
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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.