Interplay of Nutrients and Hormones in the Regulation of Glucagon Release*
Abstract
The role of nutrients and hormones in the regulation of glucagon release is investigated in pancreatic A cells purified by autofluorescence-activated cell sorting. Purified A cells lack secretory activity in 1-h incubation at 1.4 mM glucose. Their release mechanism can be activated by arginine, alanine, and glutamine, alone or in combination. Glucose inhibits amino acid-induced glucagon release through a direct insulin-independent action upon pancreatic A cells. Nutrient-induced glucagon release is suppressed by somatostatin and amplified by (Bu)2cAMP or epinephrine. The epinephrine stimulus is inhibited by 10(-11) M somatostatin and abolished by 10(-10) M of this peptide. The effects of somatostatin and epinephrine are associated with parallel changes in cellular cAMP levels, which is not the case for the variations induced by amino acids or glucose. It is confirmed that calcium is an essential requirement for glucagon release. In contrast to its exquisite sensitivity for somatostatin, the glucagon release process is relatively insensitive to insulin during a 1-h exposure. The hormone affects solely epinephrine-induced glucagon release and its inhibitory action is partial and only observed at 10(-7) M. This suppressive effect of insulin is not attributable to variations in glucose handling but appears associated with the stimulatory effect of epinephrine. It is concluded that a nutrient-induced signal interacts with a hormone-inducible cAMP signal to activate the secretory process in pancreatic A cells.
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Studies of pancreatic islets and cells have provided additional evidence that glucose regulates glucagon release by a direct effect on the alpha cell.
“and studies of pancreatic islets and cells have provided additional evidence that glucose regulates glucagon release by a direct effect on the alpha cell [5,[8][9][10][12][13][14][15][16][17].”
From Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells (2007) · cites this paper as [8]
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InfluentialGlucagon secretion and signaling in the development of diabetes
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“2b) may be mediated by a paracrine signaling mechanism similar to that of glycine (31) and/or arginine (60).”
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Widmaier, E. P., Plotsky, P. M., Sutton, S. W., & Vale, W. (1988) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1988.255.3.e287 · Cited by 45 · see citing works
McCrimmon, R. J., Evans, M. L., Jacob, R. J., Fan, X., Zhu, Y., Shulman, G. I., & Sherwin, R. S. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00195.2002 · Cited by 44 · see citing works
“secretory responses to other stimuli remaining largely intact), develops concomitantly with progressive loss of beta-cell function (21), is not affected by pharmacological blockade of classical autonomic mediators (27;53), and that isolated alpha-cells do not appear able to respond to hypoglycemia per se (40), suggest…”
BackgroundModeling the pancreatic α-cell: dual mechanisms of glucose suppression of glucagon secretion
Watts, M., & Sherman, A. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2013.11.4504 · Cited by 45 · see citing works
Is GLUT2 required for glucose sensing?
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“It has been shown that glucose inhibits (9) or, conversely, stimulates (10,11) glucagon release of isolated a-cells.”
BackgroundHomotypic cell contact enhances insulin but not glucagon secretion
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“We previously reported that 1 mol/l exendin-(9-39)-NH2 had no effect on glucagoninduced cAMP production by rat hepatocytes (8).”
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“Glucagon release by pancreatic -cells is stimulated directly by low blood glucose levels (44) or indirectly by autonomic inputs from sympathetic (NE) and parasympathetic (acetylcholine) innervations as well as adrenal medulla (EPI) (45).”
BackgroundGlucose and amino acid metabolism in mice depend mutually on glucagon and insulin receptor signaling
Galsgaard, K. D., Winther‐Sørensen, M., Pedersen, J., Kjeldsen, S. A. S., ROSENKILDE, M. M., Albrechtsen, N. J. W., & Holst, J. J. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00410.2018 · Cited by 35 · see citing works
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Characterization of a Novel Protein Kinase C Response Element in the Glucagon Gene
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“Whereas the stimulation of b-adrenergic receptors on A cells raises the cellular cyclic AMP (cAMP) levels (59, 67), the islet muscarinic acetylcholine receptors are of the M3 receptor subtype that activates phospholipase C, generating inositol 1,4,5-trisphosphate and diacylglycerol, an activator of protein kinase C is…”
BackgroundPancreatic Response to Mild Non–Insulin-Induced Hypoglycemia Does Not Involve Extrinsic Neural Input
Sherck, S. M., Shiota, M., Saccomando, J., Cardin, S., Allen, E. J., Hastings, J. R., Neal, D. W., Williams, P. E., & Cherrington, A. D. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2487 · Cited by 30 · see citing works
“Changes in blood substrate levels are also unlikely to have caused the rise in plasma glucagon levels, as glucagon secretion is stimulated by amino acids, which fell during the study, and inhibited by NEFA and ketones, which rose during the study (7,38).”
Backgroundα- and β-Cell Responses to Small Changes in Plasma Glucose in the Conscious Dog
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Glucagon‐like peptide‐1 drives energy metabolism on the synaptic highway
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Dietary carbohydrates and amino acids influence oocyte quality in dairy heifers
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Production et sécrétion de l'insuline par la cellule β pancréatique
Magnan, C., & Ktorza, A. (2005) · EMC - Endocrinologie · doi:10.1016/j.emcend.2005.07.001 · Cited by 28 · see citing works
Pax6 Is a Key Component of Regulated Glucagon Secretion
Gosmain, Y., Cheyssac, C., Masson, M. H., Guérardel, A., Poisson, C., & Philippé, J. (2012) · Endocrinology · doi:10.1210/en.2012-1425 · Cited by 27 · see citing works
- Authors
- PIPELEERS, D. G., SCHUIT, F. C., SCHRAVENDIJK, C. F. H. V., & WINKEL, M. V. D.
- Affiliations
- Vrije Universiteit Brussel (BE)
- ORCID
- PIPELEERS, D. G.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1985-09
- Volume
- 117
- Issue
- 3
- Pages
- 817-823
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W4250756743
- Cited by
- 169
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 1 · 2020: 1 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 5 · 2014: 5 · 2013: 2 · 2012: 5
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- glucagon secretion, pancreatic A cells, nutrient regulation, amino acids, glucose, somatostatin, epinephrine, cyclic AMP, insulin, calcium, pancreatic islets
- MeSH terms
- Alanine, Amino Acids, Animals, Arginine, Calcium, Bucladesine, Epinephrine, Flow Cytometry, Glucagon, Glucose, Glutamine, Islets of Langerhans, Male, Pancreatic Hormones, Rats, Inbred Strains, Somatostatin, Rats, In Vitro Techniques
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