ArticleJCI insight2021
Antagonizing somatostatin receptor subtype 2 and 5 reduces blood glucose in a gut- and GLP-1R-dependent manner.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Real-world evidence of effectiveness and safety of pasireotide in the treatment of acromegaly: a systematic review and meta-analysis.Reviews in endocrine & metabolic disorders · 2025Pooled it
- Intra-Islet Paracrine Regulation of Glucagon Secretion During Hypoglycemia, Euglycemia, and Hyperglycemia.Annals of the New York Academy of Sciences · 2026Review
- Plasma GLP-1 (Glucagon-like Peptide-1) Depletion Is Correlated with Dysregulation of Adipocytokine in Type 2 Diabetic Patients With or Without Metabolic-Associated Fatty Liver Disease (MAFLD): A Cross-Sectional Study Related to Gender-Sex Disparities.International journal of molecular sciences · 2026Article
- Prolonged Somatostatin Receptor 2 Antagonism Enhances Glucagon Response to Hypoglycemia in Male Diabetic Rats.Endocrinology · 2026Article
- Peptide-based therapeutics targeting GPCRs: recent applications in the treatment of metabolic disorders.Frontiers in pharmacology · 2026Review
- Single-cell transcriptomics of human organoid-derived enteroendocrine cell populations from the small intestine.The Journal of physiology · 2025Article
- Understanding the release mechanisms and secretion patterns for glucagon-like peptide-1 using the isolated perfused intestine as a model.Biochemical Society transactions · 2025Review
- Differential Impact of Medical Therapies for Acromegaly on Glucose Metabolism.International journal of molecular sciences · 2025Review
- Bile acids and gut microbiota: interactions and impacts on polycystic ovary syndrome.Frontiers in microbiomes · 2025Review
- Impact of hyperglycemia and antidiabetic medication on pancreatic uptake on [Frontiers in endocrinology · 2025Article
- Inhibition of somatostatin enhances the long-term metabolic outcomes of sleeve gastrectomy in mice.Molecular metabolism · 2024Article
- GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells.Peptides · 2024Article
- Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins.Frontiers in endocrinology · 2024Article
- Evaluating the effectiveness of a novel somatostatin receptor 2 antagonist, ZT-01, for hypoglycemia prevention in a rodent model of type 2 diabetes.Frontiers in pharmacology · 2024Article
- Selective somatostatin receptor 5 inhibition improves hepatic insulin sensitivity.Pharmacology research & perspectives · 2023Article
- Enhancing endogenous levels of GLP1 dampens acute olanzapine induced perturbations in lipid and glucose metabolism.Frontiers in pharmacology · 2023Article
- Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes.Frontiers in pharmacology · 2023Review
- Pterostilbene Fails to Rescue Insulin Secretion and Sensitivity in Multiple Murine Models of Diabetes.Nutrients · 2022Article
- Disrupted and Elevated Circadian Secretion of Glucagon-Like Peptide-1 in a Murine Model of Type 2 Diabetes.Endocrinology · 2022Article
- Molecular targets in acromegaly.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatostatin (SS) inhibits glucagon-like peptide-1 (GLP-1) secretion in a paracrine manner. We hypothesized that blocking somatostatin subtype receptor 2 (SSTR2) and 5 (SSTR5) would improve glycemia by enhancing GLP-1 secretion. In the perfused mouse small intestine, the selective SSTR5 antagonist (SSTR5a) stimulated glucose-induced GLP-1 secretion to a larger degree than the SSTR2 antagonist (SSTR2a). In parallel, mice lacking the SSTR5R showed increased glucose-induced GLP-1 secretion. Both antagonists improved glycemia in vivo in a GLP-1 receptor-dependent (GLP-1R-dependent) manner, as the glycemic improvements were absent in mice with impaired GLP-1R signaling and in mice treated with a GLP-1R-specific antagonist. SSTR5a had no direct effect on insulin secretion in the perfused pancreas, whereas SSTR2a increased insulin secretion in a GLP-1R-independent manner. Adding a dipeptidyl peptidase 4 inhibitor (DPP-4i) in vivo resulted in additive effects on glycemia. However, when glucose was administered intraperitoneally, the antagonist was incapable of lowering blood glucose. Oral administration of SSTR5a, but not SSTR2a, lowered blood glucose in diet-induced obese mice. In summary, we demonstrate that selective SSTR antagonists can improve glucose control primarily through the intestinal GLP-1 system in mice.
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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 Socratic graph.