ArticleAmerican journal of physiology. Endocrinology and metabolism2015
Somatostatin and insulin mediate glucose-inhibited glucagon secretion in the pancreatic α-cell by lowering cAMP.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- The relationship between glucose and the liver-alpha cell axis - A systematic review.Frontiers in endocrinology · 2022Pooled it
- Stathmin-2 mediates paracrine hormone regulation of glucagon through lysosomal trafficking in αTC1-6 cells.The Journal of physiology · 2026Article
- Intra-Islet Paracrine Regulation of Glucagon Secretion During Hypoglycemia, Euglycemia, and Hyperglycemia.Annals of the New York Academy of Sciences · 2026Review
- Increased ADORA1 expression in pancreatic islets coincides with insulin secretory defects in human type 2 diabetes.The Journal of biological chemistry · 2026Article
- Alpha cell dysfunction in type 2 diabetes: associations with insulin resistance and reduced insulin secretion.BMJ open diabetes research & care · 2026Article
- From beta-cell failure to islet dysfunction: the emerging role of the alpha cell.BMJ open diabetes research & care · 2026Article
- Differential association of hyperglucagonemia with C-peptide levels in diabetic ketosis/ketoacidosis and hyperosmolar hyperglycemic state.Diabetology international · 2026Article
- Role of complexin 2 in the regulation of hormone secretion from the islet of Langerhans.American journal of physiology. Endocrinology and metabolism · 2025Article
- Somatostatin modulation of initial fusion pores in CaThe Journal of physiology · 2025Article
- Review
- Imeglimin suppresses glucagon secretion and induces a loss of α cell identity.Cell reports. Medicine · 2025Article
- Combining a novel ensemble model and multiplex methylation SNaPshot assays for saliva age prediction and cross-platform data analysis.BMC genomics · 2025Article
- Real-time detection of somatostatin release from single islets reveals hypersecretion in type 2 diabetes.Acta physiologica (Oxford, England) · 2025Article
- Decoding the Significance of Alpha Cell Function in the Pathophysiology of Type 1 Diabetes.Cells · 2024Review
- Constitutive Pleiotrophin Deletion Results in a Phenotype with an Altered Pancreatic Morphology and Function in Old Mice.International journal of molecular sciences · 2024Article
- Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling.Diabetes · 2024Article
- CK2 activity is crucial for proper glucagon expression.Diabetologia · 2024Article
- In vitro effect of visfatin on endocrine functions of the porcine corpus luteum.Scientific reports · 2024Article
- Urocortin 3 contributes to paracrine inhibition of islet alpha cells in mice.The Journal of endocrinology · 2024Article
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The dysregulation of glucose-inhibited glucagon secretion from the pancreatic islet α-cell is a critical component of diabetes pathology and metabolic disease. We show a previously uncharacterized [Ca(2+)]i-independent mechanism of glucagon suppression in human and murine pancreatic islets whereby cAMP and PKA signaling are decreased. This decrease is driven by the combination of somatostatin, which inhibits adenylyl cyclase production of cAMP via the Gαi subunit of the SSTR2, and insulin, which acts via its receptor to activate phosphodiesterase 3B and degrade cytosolic cAMP. Our data indicate that both somatostatin and insulin signaling are required to suppress cAMP/PKA and glucagon secretion from both human and murine α-cells, and the combination of these two signaling mechanisms is sufficient to reduce glucagon secretion from isolated α-cells as well as islets. Thus, we conclude that somatostatin and insulin together are critical paracrine mediators of glucose-inhibited glucagon secretion and function by lowering cAMP/PKA signaling with increasing glucose.
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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.