Summary
The interrelationships between glucose and calcium in glucagon release were investigated using the dynamic system of the in vitro perfused rat pancreas. When calcium deprivation was induced in the presence of fixed concentrations of glucose prevailing throughout the experiments (3.3, 5.5, 8.3 and 16.6 mM), an enhancement of glucagon release invariably occurred, the shape and amplitude of such response differing in relation to the environmental glucose concentration. Such enhancement of glucagon release was readily reversible upon restoration of normal calcium levels. By contrast, during the period of calcium deprivation itself, glucagon release was little influenced by either raised (from 3.3 to 16.6 mM) or decreased (from 16.6 to 3.3 mM) glucose concentrations. These results clearly indicate that calcium plays, at least, a dual role — both inhibitory and permissivein glucagon secretion, but the intimate mechanisms by which calcium exerts such a dual action are at present unknown.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ashby, J. P., Speake, R. N.: Insulin and glucagon secretion from isolated islets of Langerhans. The effects of calcium ionophores. Biochem. J.150, 89–96 (1975)
Bhatena, S., Perrino, P., Voyles, N., Smith, S., Wilkins, S., Coy, D. H., Schally, A., Recant, L.: Reversal of somatostatin inhibition of insulin and glucagon secretion. Diabetes24 (Suppl. 2), 408 (1975)
Böttger, I., Faloona, G. R., Unger, R. H.: The effect of calcium and other salts upon the release of glucagon-like immunoreactivity (GLI) from the gut. J. clin. Invest.51, 831–836 (1972)
Edwards, J. C.: A-cell metabolism and glucagon secretion. Postgrad. med. J.49 (August Suppl.), 611–615 (1973)
Edwards, J. C., Hellerström, C., Petersson, B., Taylor, K. W.: Oxidation of glucose and fatty acids in normal and in A2-cell rich pancreatic islets from guinea-pigs. Diabetologia8, 93–98 (1972)
Edwards, J. C., Howell, S. L.: Effects of vinblastine and colchicine on the secretion of glucagon from isolated guinea-pig islets of Langerhans. FEBS Letters30, 89–92 (1973)
Frankel, B. J., Gerich, J. E., Hagura, R., Fanska, R. E., Gerritsen, G. G., Grodsky, G. M.: Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster. J. clin. Invest.53, 1637–1646 (1974)
Gerich, J. E., Frankel, B. J., Fanska, R., West, L., Forsham, P. H., Grodsky, G. M.: Calcium dependency of glucagon secretion from the in vitro perfused rat pancreas. Endocrinology94, 1381–1385 (1974)
Grodsky, G. M.: A threshold distribution hypothesis for packet storage of insulin. II. Effect of calcium. Diabetes21 (Suppl. 2), 584–593 (1972)
Howell, S. L., Whitfield, M.: Cytochemical localization of adenylate cyclase activity in rat islets of Langerhans. J. Histochem. Cytochem.20, 873–879 (1972)
Howell, S. L., Edwards, J. G., Montague, W.: Regulation of adenylate cyclase and cyclic-AMP protein kinase activities in A2-cell rich guinea-pig islets of Langerhans. Horm. Metab. Res.6, 49–52 (1974)
Kuzuya, T., Kajinuma, H., Ide, T.: Effect of intrapancreatic injection of potassium and calcium on insulin and glucagon secretion in dogs. Diabetes23, 55–60 (1974)
Leclercq-Meyer, V., Marchand, J., Leclercq, R., Malaisse, W. J.: Glucagon and insulin release by the in vitro perfused rat pancreas. Influence of the colloid composition of the perfusate. Diabète Métab.2, 57–65 (1976)
Leclercq-Meyer, V., Marchand, J., Malaisse, W. J.: The effect of calcium and magnesium on glucagon secretion. Endocrinology93, 1360–1370 (1973)
Leclercq-Meyer, V., Marchand, J., Malaisse, W. J.: Possible role of a microtubular-microfilamentous system in glucagon secretion. Diabetologia10, 215–224 (1974)
Leclercq-Meyer, V., Marchand, J., Rebolledo, O., Malaisse, W. J., Leclercq, R.: A combined radioimmunoassay for glucagon and insulin. Diabetologia11, 419–425 (1975)
Leclercq-Meyer, V., Rebolledo, O., Marchand, J., Malaisse, W. J.: Glucagon release: Paradoxical stimulation by glucose during calcium deprivation. Science189, 897–899 (1975)
Loewenstein, W. R.: Permeability of membrane junctions. Ann. N.Y. Acad. Sci.137, 441–472 (1966)
Loubatières, A., Mariani, M. M., Ribes, G., de Malbosc, G., Chapal, J.: Etude expérimentale d'un nouveau sulfamide hypoglycémiant particulièrement actif, le HB 419 ou glibenclamide. I. Action betacytotrope et insulino-sécrétrice. Diabetologia5, 1–10 (1969)
Lundqvist, G.: Enzymatic studies of glucose phosphorylation in the glucagon producing cells of the duck pancreas. Horm. Metab. Res.4, 83–86 (1972)
Malaisse, W. J.: Hormonal and environmental modification of islet activity. In: Handbook of physiology. Section 7: Endocrinology 1: Endocrine Pancreas (eds. N. Freinkel, D. F. Steiner), pp. 237–260. Washington, D. C.: American Physiological Society 1972
Nonaka, K., Sugase, T., Foa, P. P.: Glucagon release by the isolated pancreatic islets of the Syrian Hamster. In: Proceedings of the Seventh Congress of the International Diabetes Federation (eds. R. R. Rodriguez, J. Vallance-Owen), Excerpta med. Intern. Congr. Ser. (Amst.)231, 625–35 (1971)
Ohneda, A., Matsuda, K., Horigome, K., Ishii, S., Yamagata, S.: Effect of intrapancreatic administration of calcium upon glucagon secretion in dogs. Tohoku J. exp. Med.113, 301–311 (1974)
Orci, L., Blondel, B., Malaisse-Lagae, F., Ravazzola, M., Wollheim, C., Malaisse, W. J., Renold, A. E.: Cell motility and insulin release in monolayer cultures of endocrine pancreas. Diabetologia10, 382 (1974)
Orci, L., Malaisse-Lagae, F., Ravazzola, M., Rouiller, D., Renold, A. E., Perrelet, A., Unger, R. H.: A morphologic basis for intercellular communication betweenα- andβ-cells in the endocrine pancreas. J. clin. Invest.56, 1066–1070 (1975)
Pagliara, A. S., Stillings, S. N., Haymond, M. W., Hover, B. H., Matschinsky, F. M.: Insulin and glucose as modulators of the amino acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. J. clin. Invest.55, 244–255 (1975)
Pagliara, A. S., Stillings, S. N., Hover, B., Martin, D. M., Matschinsky, F. M.: Glucose modulation of amino acid-induced glucagon and insulin release in the isolated perfused rat pancreas. J. clin. Invest.54, 819–832 (1974)
Randle, P. J., Hales, C. N.: Insulin release mechanisms. In: Handbook of Physiology. Section 7: Endocrinology 1: Endocrine Pancreas (eds. N. Freinkel, D. F. Steiner), pp. 219–235. Washington, D. C.: American Physiological Society 1972
Rebolledo, O., Leclercq-Meyer, V., Marchand, J., Leclercq, R., Malaisse, W. J.: Failure of parathormone to affect insulin and glucagon release from the perfused rat pancreas. Horm. Metab. Res.7, 287–290 (1975)
Snedecor, G. W.: Statistical methods. Ames: Iowa State University Press 1956
Unger, R. H., Lefebvre, P. J.: Glucagon physiology. In: Glucagon, molecular physiology, clinical and therapeutic implications (eds. P. J. Lefebvre, R. H. Unger), pp. 213–244. Oxford: Pergamon Press 1972
Van Obberghen, E., Somers, G., Devis, G., Ravazzola, M., Malaisse-Lagae, F., Orci, L., Malaisse, W. J.: Dynamics of insulin release and microtubular-microfilamentous system. VII. Do microfilaments provide the motive force for the translocation and extrusion of beta granules? Diabetes24, 892–901 (1975)
Weir, G. C., Knowlton, S. D., Martin, D. B.: Glucagon secretion from the perfused rat pancreas. Studies with glucose and catecholamines. J. clin. Invest.54, 1403–1412 (1974)
Wollheim, C. B., Blondel, B., Müller, W. A., Sharp, G. W. G.: Relation of Ca++ to cyclic AMP induced alterations of glucagon release in pancreatic monolayer cultures. Europ. J. clin. Invest.5, 58P (1975)
Wollheim, G., Blondel, B., Sharp, G. W. G.: Insulin and glucagon release in pancreatic monolayer cultures: Effect of calcium and ionophore A23187. Diabetologia10, 391 (1974)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Leclercq-Meyer, V., Marchand, J. & Malaisse, W.J. The role of calcium in glucagon release, interactions between glucose and calcium. Diabetologia 12, 531–538 (1976). https://doi.org/10.1007/BF01219520
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01219520