Summary
Previously, we reported that change from the normal pH of 7.4 surrounding the islet cells to 7.8 results in a decreased B-cell response to 16.6 mM glucose, 10 mM arginine or 400 µg/ml tolbutamide. In the present report we studied the effect of modifications in the extracellular pH on glucose- and arginine-induced glucagon and insulin secretion by the perfused rat pancreas. It was found that at pH 7.8, arginine-induced glucagon secretion was significantly greater than at pH 7.4. On the other hand, the switch from pH 7.4 to 7.8 in a pancreas already stimulated by either low glucose or arginine, produced fast and transient glucagon release. Sequential extracellular pH changes from 7.4 to 7.8 and back to 7.4 in the presence of 8.3 mM glucose and a 5 mM arginine stimulus demonstrated that A- and B-cells rapidly modify their secretion in response to extracellular alkalosis in opposite directions. While glucagon output was enhanced (mean secretory rates at pH 7.4, 0.692 ± 0.042 ng/min and 0.948 ± 0.57 at pH 7.8), insulin secretion was clearly reduced (72.6 ± 6.2 ng/min and 35.7 ± 2.8 ng/min at pH 7.4 and 7.8, respectively). The above observations, together with our previously reported data, indicate that extracellular pH plays an important role in the regulation of glucagon and insulin release. Particularly, extracellular alkalosis enhances A-cell response to 2.3 mM glucose and 5 mM arginine while partially inhibiting B-cell secretion in the perfused rat pancreas.
Similar content being viewed by others
References
Gerich J. E., Frankel B. J., Fanska R., West L., Forsham P. H., Grodsky G. M.: Calcium dependency of glucagon secretion from thein vitro perfused rat pancreas — Endocrinology94, 1381, 1974.
Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J.: Coated-charcoal immunoassay of insulin — J. clin. Endocr.25, 1375, 1965.
Hutton J. C., Sener A., Herchuelz A., Valverde I., Boschero A. C., Malaisse W. J.: The stimulus-secretion coupling of glucose-induced insulin release. XLII. Effects of extracellular pH on insulin release: their dependency on nutrient concentration — Hormone metab. Res.12, 294, 1980.
Iversen J., Hermansen K.: Calcium, glucose and glucagon release — Diabetologia13, 297, 1977.
Jørgensen K. H., Larsen U. D.: Purification of125I-glucagon by anion exchange chromatography — Hormone metab. Res.4, 223, 1972.
Leclercq-Meyer V., Marchand J., Leclercq R., Malaisse W. J.: Glucagon and insulin release by thein vitro perfused rat pancreas. Influence of the colloid composition of the perfusate — Diabèté et Métab.2, 57, 1976.
Leclercq-Meyer V., Marchand J., Malaisse W. J.: The role of calcium in glucagon release, interactions between glucose and calcium — Diabetologia12, 531, 1976.
Leclercq-Meyer V., Rebolledo O. R., Marchand J., Malaisse W. J.: Glucagon release: paradoxical stimulation by glucose during calcium deprivation — Science189, 897, 1975.
Matschinsky F. M., Pagliara A. S., Hover B. A., Pace C. S., Ferendelli J. A., Williams A.: Hormone secretion and glucose metabolism in islets of Langerhans of the isolated perfused pancreas from normal and streptozotocin diabetic rats — J. biol. Chem.251, 6053, 1976.
Pedersen K. O.: Binding of calcium to serum albumin. II. Effect of pH via competitive hydrogen and calcium ion binding to the imidazole groups of albumin — Scand. J. clin. Lab. Invest.29, 75, 1972.
Petersson B., Hellerström C., Gunnarsson R.: Structure and metabolism of the pancreatic islets in streptozotocin treated guinea pigs — Hormone metab. Res.2, 313, 1970.
Rebolledo O. R., Gutierrez A. M., Gagliardino J. J.: Characteristics of the inhibitory effect of alkalosis on insulin secretion — Acta physiol. lat-amer. (In press).
Rebolledo O. R., Hernández R. E., Gagliardino J. J.: Insulin secretion during acid-base alterations. III. Role of extracellular calcium on the blocking effect of alkalosis — Acta physiol. lat-amer.30, 117, 1980.
Rebolledo O. R., Hernández R. E., Gagliardino J. J.: Effect of acid-base alterations on glucagon and insulin secretion by the perfused rat pancreas — IRCS, Med. Sci. Physiol.9, 745, 1981.
Rebolledo O. R., Hernández R. E., Gagliardino J. J.: Effect of pCO2 induced acid-base alterations on insulin secretion by perfused rat pancreas — IRCS, Med. Sci. Physiol.9, 98, 1981.
Rebolledo O. R., Hernández R. E., Zanetta A. C., Gagliardino J. J.: Insulin secretion during acid-base alterations — Amer. J. Physiol.234, E426, 1978.
Schaer H.: Decrease in ionized calcium by bicarbonate in physiological solutions — Pflügers Arch. ges. Physiol.347, 249, 1974.
Unger R. H.: Diabetes and the alpha cell — Diabetes25, 136, 1976.
Unger R. H., Raskin P., Srikant C. B., Orci L.: Glucagon and the A-cells — Recent Progr. Hormone Res.33, 477, 1977.
Wollheim C. B., Blondel B., Renold A. E., Sharp G. W. G.: Calcium induced glucagon release in monolayer culture of the endocrine pancreas. Studies with ionophore A23187 — Diabetologia12, 287, 1976.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rebolledo, O.R., Gagliardino, J.J. Glucagon and insulin secretion during acid-base alterations. Acta diabet. lat 20, 211–220 (1983). https://doi.org/10.1007/BF02581265
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02581265