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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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“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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Liu, W. X., Kin, T., Ho, S., Dorrell, C., Campbell, S. R., Luo, P., & Chen, X. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.11.018 · Cited by 27
“However, both inhibitory [77] and stimulatory [36,37] effects of glucose on glucagon secretion from the purified rodent a-cells have been reported, and the underlying mechanisms are still disputed.”
BackgroundTonolo, G., Melis, M. G., Ciccarese, M., Secchi, G., Atzeni, M. M., Maioli, M., Pala, G., Massidda, A., Manai, M., Pilosu, R., et al. (1997) · Diabetologia · doi:10.1007/s001250050647 · Cited by 22
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Carnegie, J. R., Robert, C. E., Wu, J., Young, R., Wolf, B. A., & Burkhardt, B. R. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.05.008 · Cited by 21
Knepel, W., Chafitz, J., & Habener, J. F. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.12.6799-6804.1990 · Cited by 20
Hii, C. S. T., & Howell, S. L. (1987) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(87)90075-x · Cited by 20
Wesslén, N., PIPELEER, D., Winkel, M. V. D., Rorsman, P., & Hellman, B. (1987) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1987.tb08231.x · Cited by 18
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Thermos, K., Meglasson, M. D., Nelson, J., et al. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.2.e216 · Cited by 17
Distinct Classes of Central GLUT2-Dependent Sensors Control Counterregulation and Feeding
Marty, N., Bady, I., & Thorens, B. (2006) · Diabetes · doi:10.2337/db06-s014 · Cited by 17
“The secretory activity of the -cells is regulated by an -cell glucose sensor (22), by intra-islet insulin secretion (23), by the sympathetic and parasympathetic autonomic nervous systems, and by the sympathoadrenal axis (24).”
BackgroundTakahashi, R., Ishihara, H., Tamura, A., Yamaguchi, S., Yamada, T., Takei, D., Katagiri, H., Endou, H., & Oka, Y. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00131.2005 · Cited by 16
“Nonetheless, an earlier study has found important characteristics of -cells (32), and several recent studies have discovered interesting features of this cell type.”
BackgroundKatoh, K., Asari, M., Ishiwata, H., Sasaki, Y., & Obara, Y. (2003) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpb.2003.10.011 · Cited by 17
Regulation of GAD expression in islets of Langerhans occurs both at the mRNA and protein level
Velloso, L. A., Björk, E., Ballagi, A. E., et al. (1994) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(94)90094-9 · Cited by 15
McCarty, M. F. (1996) · Medical Hypotheses · doi:10.1016/s0306-9877(96)90004-3 · Cited by 14
Amino acids and the changing face of the α-cell
Hamilton, A., Eliasson, L., & Knudsen, J. G. (2023) · Peptides · doi:10.1016/j.peptides.2023.171039 · Cited by 14
“Follow-up studies then measured the effect of individual amino acids in dogs [24], and sheep [25] showing most amino acids stimulate glucagon secretion and that they have synergistic effects when added together [26].”
BackgroundHistidine Availability Alters Glucagon Gene Expression in Murine αTC6 Cells
Paul, G. L., Waegner, A., Gaskins, H. R., & Shay, N. F. (1998) · Journal of Nutrition · doi:10.1093/jn/128.6.973 · Cited by 13
Insulin Sensitively Controls the Glucagon Response to Mild Hypoglycemia in the Dog
Igawa, K., Mugavero, M., Shiota, M., Neal, D. W., & Cherrington, A. D. (2002) · Diabetes · doi:10.2337/diabetes.51.10.3033 · Cited by 13
“It is known that amino acids have stimulatory effects and that FFAs and ketones have inhibitory effects on glucagon secretion from the -cell (34,48,49).”
BackgroundXu, L., Hanigan, M. D., Lin, X., Li, M., Yan, Z., Hu, Z., Hou, Q., Wang, Y., Shi, K., & Wang, Z. (2019) · Journal of Dairy Science · doi:10.3168/jds.2018-16102 · Cited by 12
Chapter 21 Pancreatic Network Control of Glucagon Secretion and Counterregulation
Farhy, L. S., & McCall, A. L. (2009) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(09)67021-x · Cited by 12
Taira, A., Arita, E., Matsumoto, E., Oohira, A., Iwase, K., Hiwasa, T., Yokote, K., Shibata, S., & Takiguchi, M. (2019) · Chronobiology International · doi:10.1080/07420528.2019.1570246 · Cited by 11
“As for the factor(s) raising glucagon levels on the high-protein diets, amino acids themselves are also remarkable, since they directly stimulate glucagon secretion from the perfused dog pancreas (Ipp et al. 1977) and isolated rat α-cells (Pipeleers et al. 1985).”
BackgroundSgambato, S., Paolisso, G., Passariello, N., et al. (1987) · European Journal of Clinical Pharmacology · doi:10.1007/bf00637673 · Cited by 10
“Thus, combined administration of glucose+sparteine could stimulate and potentiate fl-cells, while a-cells, whose secretion is also Ca + + dependent [13, 14], are probably stimulated by sparteine and inhibited by glucose and insulin.”
BackgroundResponses of the pancreatic A cell during hypoglycemia and hyperglycemia are dependent on the B cell
McCulloch, D. K., Raghu, P., Koerker, D. J., Palmer, J. P., & Klaff, L. J. (1989) · Metabolism · doi:10.1016/0026-0495(89)90111-x · Cited by 10
Restoration of the A cell response to glucose in isolated rat islets of Langerhans
Hii, C. S. T., & Howell, S. L. (1986) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(86)90042-0 · Cited by 10
König, W. (2000) · Ullmann's Encyclopedia of Industrial Chemistry · doi:10.1002/14356007.a19_061 · Cited by 11
The relationship between glucose and the liver-alpha cell axis – A systematic review
Pixner, T., Stummer, N., Schneider, A.-M., Lukas, A., Gramlinger, K., Julian, V., Thivel, D., Mörwald, K., Mangge, H., Dalus, C., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1061682 · Cited by 9
Role of pancreatic somatostatin in determining glucagon response to arginine and morphine
Klaff, L. J., & Taborsky, G. J. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.252.6.e751 · Cited by 9
Shiota, D., Kasamatsu, T. S., Dib, S. A., Chacra, A. R., & Moisés, R. S. (2002) · Pancreas · doi:10.1097/00006676-200205000-00010 · Cited by 8
Ito, K., Hirose, H., Kido, K., Koyama, K., Maruyama, H., & Saruta, T. (1995) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(95)01189-7 · Cited by 8
Rastogi, K. S., BRUBAKER, P. L., Kawasaki, A., et al. (1993) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y93-074 · Cited by 8
Glucose-induced secretion of ACTH-like products by rat pancreatic islets
Borelli, M. I., Morano, M. I., Estivariz, F. E., et al. (1994) · Archives of Physiology and Biochemistry · doi:10.3109/13813459408996100 · Cited by 8
Hepatic CBP/p300 Orchestrate Amino Acid‐Driven Gluconeogenesis through Histone Crotonylation
Sheng, C., Li, T., Lin, H., Ma, X., Zhou, F., Li, M., Wang, Y., Wang, S., Tan, J., Chen, J. Y., et al. (2025) · Advanced Science · doi:10.1002/advs.202507635 · Cited by 9
Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells
Gilon, P., Cheng, R., Lai, B. K., Chae, H., & Gómez-Ruiz, A. (2014) · Springer eBooks · doi:10.1007/978-94-007-6884-0_37-2 · Cited by 8
Role of protein kinase C in the regulation of glucagon gene expression by arginine
Yamato, E., Ikegami, H., Tahara, Y., et al. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91230-p · Cited by 6
Kisanuki, K., Kishikawa, H., Araki, E., et al. (1995) · Diabetologia · doi:10.1007/s001250050301 · Cited by 6
PIPELEERS, D. G., & Winkel, M. V. D. (1989) · Elsevier eBooks · doi:10.1016/b978-0-12-417760-4.50028-8 · Cited by 6
Self-citationGlucagon mediates arginine-induced somatostatin secretion from isolated rat pancreatic islets
Vonen, B., Florholmen, J. R., Malm, D., Torjessen, P., & BURHOL, P. G. (1992) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365519209088773 · Cited by 6
Kofod, H., Holst, J. J., & Lernmark, Å. (1988) · Regulatory Peptides · doi:10.1016/0167-0115(88)90232-7 · Cited by 5
Intestinal Proglucagon-Derived Peptides
Brubaker, P. L., & Drucker, D. J. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-695-9_20 · Cited by 5
Impact of Dietary Proteins on Energy Balance, Insulin Sensitivity and Glucose Homeostasis
Chevrier, G., Mitchell, P. L., Beaudoin, M., & Marette, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802167-5.00018-9 · Cited by 5
Liu, D., Adamson, U., Lins, P. E., & CLAUSEN‐SJÖBOM, N. (1993) · Diabetic Medicine · doi:10.1111/j.1464-5491.1993.tb00052.x · Cited by 4
Chen, X., Hermansen, K., & Jeppesen, P. B. (2012) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2012.01633.x · Cited by 4
“AAs are well-known acute stimuli of glucagon [21,22] and insulin secretion [23].”
BackgroundGustavson, S. M., Nishizawa, M., Farmer, B., Neal, D. W., Briššová, M., Powers, A. C., & Cherrington, A. D. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00321-4 · Cited by 4
Chendrimada, T. P., Adams, K. A., Freeman, M. E., et al. (2006) · Poultry Science · doi:10.1093/ps/85.4.753 · Cited by 4
Glucagon and Glucagon‐like Peptide Production and Degradation
Kieffer, T. J., Hussain, M. A., & Habener, J. F. (2001) · Comprehensive physiology · doi:10.1002/cphy.cp070208 · Cited by 4
Gronau, K. A., & Brubaker, P. L. (1995) · Endocrine · doi:10.1007/bf02935683 · Cited by 4
Nutrition in adolescent, puberty, and young girls
Uddin, M. J., Sadiq, S. B., Sejuti, S. R., Upoma, N. J., & Shanaz, B. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-34003-1.00013-4 · Cited by 3
Ferreira, B., Heredia, A., & Serpa, J. (2023) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2023.112063 · Cited by 3
Xu, J., Zhu, R., Chen, Y., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202401945r · Cited by 3
Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells
Gilon, P., Cheng, R., Lai, B. K., Chae, H., & Gómez-Ruiz, A. (2014) · Springer eBooks · doi:10.1007/978-94-007-6686-0_37 · Cited by 3
Chapter 7 Molecular aspects of the glucagon gene
Laser, B., & Philippé, J. (1997) · Advances in molecular and cellular endocrinology · doi:10.1016/s1569-2566(97)80038-5 · Cited by 3
Galsgaard, K. D., Jepsen, S. L., Kjeldsen, S. A. S., Pedersen, J., Albrechtsen, N. J. W., & Holst, J. J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/792119 · Cited by 3
Panzer, J., Lang, A., Levi, N. J., Garcia, P., Barro-Soria, R., & Caicedo, A. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117068 · Cited by 1
“3,36,40 However, receptors for SST, 5-HT, and GABA can also converge on a shared inhibitory mechanism, namely GIRK channels.”
Inhibition of protein kinase A—Induced glucagon synthesis and secretion by glucose
Stobie-Hayes, K. M., & Brubaker, P. L. (1996) · Metabolism · doi:10.1016/s0026-0495(96)90289-9 · Cited by 2
GLP-1 Receptors in Golden Syrian Hamster Islets: Identification and Functional Characterization
Rosselin, G., Leclercq-Meyer, V., Boissart, C., Pessah, M., & Malaisse, W. J. (1998) · Endocrine · doi:10.1385/endo:8:3:323 · Cited by 2
Park, J. H., Bae, J. G., Kim, S., Kim, C. S., Lee, S. L., & Kim, H. S. (2016) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2016.21.2.86 · Cited by 2
Metabolic effects of glucocorticoids in sheep ‐ studies with a long‐acting somatostatin analogue
Holtenius, K., & Holtenius, P. (1996) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/j.1439-0396.1996.tb00693.x · Cited by 2
Separation of Pancreatic Islet Cells according to Functional Characteristics
PIPELEERS, D. G., & Winkel, M. V. D. (1987) · Elsevier eBooks · doi:10.1016/b978-0-12-564505-8.50011-3 · Cited by 2
Self-citationTRPM7 kinase regulates α-cell proliferation and glucagon production in mice
Boulassel, S., Schreier, P. C. F., Beck, A., Choi, H., Melyshi, A. M., Reinach, P. S., Duraj, M., Vinogradov, M., Suleimen, B., Berger, J., et al. (2026) · Molecular Metabolism · doi:10.1016/j.molmet.2026.102317 · Cited by 1
“This defect is of particular significance given that nutrient availability, especially amino acids such as arginine, alanine, and glutamine, potentiates glucagon release through nutrient-sensing pathways, including mTORC1 [2,31].”
Fundamentals of Fuel Sensing and Intermediary Metabolism in Pancreatic A-and B-Cells
Li, G., Kesavan, P., Najafi, H., et al. (1994) · Humana Press eBooks · doi:10.1007/978-1-4612-0241-7_8 · Cited by 1
Drews, G. (1996) · Springer eBooks · doi:10.1007/978-3-642-60946-6_67 · Cited by 2
Dietary proteins : their effect on insulin and glucagons in relation to body weight management
Claessens, M. (2008) · Research Publications (Maastricht University) · doi:10.26481/dis.20080116mc · Cited by 1
Ahmad, M., Wu, S., Guo, X., Perrimon, N., & He, L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.04.583442 · Cited by 1
Secretion and Radioimmunoassay of Somatostatin: In Vitro System
Vonen, B., & Florholmen, J. R. (1991) · Methods in neurosciences · doi:10.1016/b978-0-12-185261-0.50024-1
Role of glutamate in regulating hypothalamic proglucagon-derived peptide secretion in vitro
Stobie-Hayes, K. M., & Brubaker, P. L. (1995) · Life Sciences · doi:10.1016/0024-3205(95)00084-4
Glucagon Switches between GLP-1 and Glucagon Receptors in Normal and Hyperglycemic MicePreprint
Han, C., Zhang, Y., Zhu, W., Yang, G., Peng, X., Mehta, S., Zhang, J., Liu, Y., & Chen, L. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3273389
Schuit, F. C. (2010) · Bohn Stafleu van Loghum eBooks · doi:10.1007/978-90-313-8225-5_12
Self-citationProduction et sécrétion de l’insuline par la cellule β pancréatique
Karaca, M., & Magnan, C. (2013) · EMC - Endocrinologie - Nutrition · doi:10.1016/s1155-1941(13)58044-9
Post-Inhibitory Rebound by δ-Cells Converts Inhibition into Excitation and Confers Islet PlasticityPreprint
Tamayo, A., Rodriguez, D. H., Pereira, E., Camacho-Becerra, S., Gonçalves, L. M., Bergreen, P.-O., Sokolov, M., Drigo, R. A. E., Alcazar, O., & Rodriguez‐Diaz, R. (2025) · SSRN Electronic Journal · doi:10.1101/2025.11.10.687745
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Iida, T., Nii, S., Nishikawa, H., Kodama, E., Imai, H., Hashizume, M., Tadokoro, R., Sugisawa, C., Iizaka, T., Otsuka, F., et al. (2025) · Diabetology International · doi:10.1007/s13340-025-00852-8
“Glicen - tin, GRPP, oxyntomodulin, and other peptides are formed in intestinal tract L cells [ 1]. hyperglycemia and facilitated in hypoglycemia [2, 5–7].”
CD98hc marks a precursor of human stem cell-derived alpha cells primed for functional maturation
Lewis-Brinkman, S., Salomon, T., Knofczynski, K. R., Duffy, C., & Peterson, Q. P. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1923474
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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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