Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1984 Mar 15;218(3):887–892. doi: 10.1042/bj2180887

Effect of glucose on the intracellular pH of pancreatic islet cells.

P Lindström, J Sehlin
PMCID: PMC1153419  PMID: 6372786

Abstract

To characterize the effect of glucose on the intracellular pH (pHi) of pancreatic islet cells, we measured the accumulation of 14C-labelled 5,5-dimethyloxazolidine-2,4-dione ( [14C]DMO) in beta-cell-rich islets from ob/ob mice. D-Glucose (20 mM) stimulated insulin release and enhanced the [14C]DMO equilibrium uptake corresponding to an increase of pHi by about 0.15 unit. The glucose effect on DMO uptake was concentration-dependent, with half-maximal effect at about 4 mM-glucose and maximum effect at about 10 mM-glucose. It was inhibited by 20 mM-mannoheptulose and potentiated by 4 mM-L-5-hydroxytryptophan, but not affected by 2 mM-theophylline. Mannoheptulose is an inhibitor and L-5-hydroxytryptophan and theophylline are potentiators of glucose-stimulated insulin release. The glucose-induced increase in pHi appeared rapidly (7 min) and persisted for at least 30 min and it was observed both in bicarbonate/CO2-buffered and in Hepes [4-(2-hydroxyethyl)-1-piperazine-ethanesulphonic acid]-buffered media. Addition of extracellular bicarbonate buffer lowered the pHi, but did not affect basal insulin release, whereas 5 mM-NH4+ increased pHi and induced a 4-fold increase of basal insulin release. We conclude that, in contrast with previous assumptions, glucose increases intracellular pH in the islet cells. This effect may be coupled to the glucose metabolism and associated with triggering of insulin release.

Full text

PDF
887

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahamsson H., Gylfe E. Demonstration of a proton gradient across the insulin granule membrane. Acta Physiol Scand. 1980 May;109(1):113–114. doi: 10.1111/j.1748-1716.1980.tb06573.x. [DOI] [PubMed] [Google Scholar]
  2. Ashcroft S. J., Hedeskov C. J., Randle P. J. Glucose metabolism in mouse pancreatic islets. Biochem J. 1970 Jun;118(1):143–154. doi: 10.1042/bj1180143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashcroft S. J., Weerasinghe L. C., Bassett J. M., Randle P. J. The pentose cycle and insulin release in mouse pancreatic islets. Biochem J. 1972 Feb;126(3):525–532. doi: 10.1042/bj1260525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ashcroft S. J., Weerasinghe L. C., Randle P. J. Interrelationship of islet metabolism, adenosine triphosphate content and insulin release. Biochem J. 1973 Feb;132(2):223–231. doi: 10.1042/bj1320223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coore H. G., Randle P. J. Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. Biochem J. 1964 Oct;93(1):66–78. doi: 10.1042/bj0930066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Deleers M., Lebrun P., Malaisse W. J. Increase in CO3H- influx and cellular pH in glucose-stimulated pancreatic islets. FEBS Lett. 1983 Apr 5;154(1):97–100. doi: 10.1016/0014-5793(83)80882-5. [DOI] [PubMed] [Google Scholar]
  7. Feldman J. M., Lebovitz H. E. Ammonium ion, a modulator of insulin secretion. Am J Physiol. 1971 Oct;221(4):1027–1032. doi: 10.1152/ajplegacy.1971.221.4.1027. [DOI] [PubMed] [Google Scholar]
  8. Hellman B., Idahl L. A., Danielsson A. Adenosine triphosphate levels of mammalian pancreatic B cells after stimulation with glucose and hypoglycemic sulfonylureas. Diabetes. 1969 Aug;18(8):509–516. doi: 10.2337/diab.18.8.509. [DOI] [PubMed] [Google Scholar]
  9. Hellman B., Idahl L. A., Lernmark A., Täljedal I. B. The pancreatic beta-cell recognition of insulin secretagogues: does cyclic AMP mediate the effect of glucose? Proc Natl Acad Sci U S A. 1974 Sep;71(9):3405–3409. doi: 10.1073/pnas.71.9.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hellman B., Idahl L. A., Sehlin J., Täljedal I. B. Influence of anoxia on glucose metabolism in pancreatic islets: lack of correlation between fructose-1,6-diphosphate and apparent glycolytic flux. Diabetologia. 1975 Dec;11(6):495–500. doi: 10.1007/BF01222098. [DOI] [PubMed] [Google Scholar]
  11. Hellman B., Sehlin J., Täljedal I. B. The intracellular pH of mammalian pancreatic -cells. Endocrinology. 1972 Jan;90(1):335–337. doi: 10.1210/endo-90-1-335. [DOI] [PubMed] [Google Scholar]
  12. Hellman B., Sehlin J., Täljedal I. B. Transport of -aminoisobutyric acid in mammalian pancretic -cells. Diabetologia. 1971 Aug;7(4):256–265. doi: 10.1007/BF01211878. [DOI] [PubMed] [Google Scholar]
  13. Hellman B. Studies in obese-hyperglycemic mice. Ann N Y Acad Sci. 1965 Oct 8;131(1):541–558. doi: 10.1111/j.1749-6632.1965.tb34819.x. [DOI] [PubMed] [Google Scholar]
  14. Lebrun P., Malaisse W. J., Herchuelz A. Effect of the absence of bicarbonate upon intracellular pH and calcium fluxes in pancreatic islet cells. Biochim Biophys Acta. 1982 Dec 30;721(4):357–365. doi: 10.1016/0167-4889(82)90090-8. [DOI] [PubMed] [Google Scholar]
  15. Lernmark A. [Isolated mouse islets as a model for studying insulin release]. Acta Diabetol Lat. 1971 Jul-Aug;8(4):649–679. doi: 10.1007/BF01550894. [DOI] [PubMed] [Google Scholar]
  16. Lindström P., Sehlin J. Opposite effects of 5-hydroxytryptophan and 5-hydroxytryptamine on the function of microdissected ob/ob-mouse pancreatic islets. Diabetologia. 1983 Jan;24(1):52–57. doi: 10.1007/BF00275948. [DOI] [PubMed] [Google Scholar]
  17. Malaisse W. J., Herchuelz A., Sener A. The possible significance of intracellular pH in insulin release. Life Sci. 1980 Apr 28;26(17):1367–1371. doi: 10.1016/0024-3205(80)90038-7. [DOI] [PubMed] [Google Scholar]
  18. Malaisse W. J., Hutton J. C., Kawazu S., Herchuelz A., Valverde I., Sener A. The stimulus-secretion coupling of glucose-induced insulin release. XXXV. The links between metabolic and cationic events. Diabetologia. 1979 May;16(5):331–341. doi: 10.1007/BF01223623. [DOI] [PubMed] [Google Scholar]
  19. Malaisse W. J., Malaisse-Lagae F., Mayhew D. A possible role for the adenylcyclase system in insulin secretion. J Clin Invest. 1967 Nov;46(11):1724–1734. doi: 10.1172/JCI105663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Malaisse W. J., Sener A., Herchuelz A., Hutton J. C. Insulin release: the fuel hypothesis. Metabolism. 1979 Apr;28(4):373–386. doi: 10.1016/0026-0495(79)90111-2. [DOI] [PubMed] [Google Scholar]
  21. Pace C. S., Sachs G. Glucose-induced proton uptake in secretory granules of beta-cells in monolayer culture. Am J Physiol. 1982 May;242(5):C382–C387. doi: 10.1152/ajpcell.1982.242.5.C382. [DOI] [PubMed] [Google Scholar]
  22. Pace C. S., Tarvin J. T., Smith J. S. Stimulus-secretion coupling in beta-cells: modulation by pH. Am J Physiol. 1983 Jan;244(1):E3–18. doi: 10.1152/ajpendo.1983.244.1.E3. [DOI] [PubMed] [Google Scholar]
  23. Roos A., Boron W. F. Intracellular pH. Physiol Rev. 1981 Apr;61(2):296–434. doi: 10.1152/physrev.1981.61.2.296. [DOI] [PubMed] [Google Scholar]
  24. Sehlin J. Interrelationship between chloride fluxes in pancreatic islets and insulin release. Am J Physiol. 1978 Nov;235(5):E501–E508. doi: 10.1152/ajpendo.1978.235.5.E501. [DOI] [PubMed] [Google Scholar]
  25. Sehlin J. Univalent ions in islet cell function. Horm Metab Res Suppl. 1980;Suppl 10:73–80. [PubMed] [Google Scholar]
  26. Sener A., Hutton J. C., Kawazu S., Boschero A. C., Somers G., Devis G., Herchuelz A., Malaisse W. J. The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets. J Clin Invest. 1978 Oct;62(4):868–878. doi: 10.1172/JCI109199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sener A., Malaisse W. J. Measurement of lactic acid in nanomolar amounts. Reliability of such a method as an index of glycolysis in pancreatic islets. Biochem Med. 1976 Feb;15(1):34–41. doi: 10.1016/0006-2944(76)90072-7. [DOI] [PubMed] [Google Scholar]
  28. Smith J. S., Pace C. S. Modification of glucose-induced insulin release by alteration of pH. Diabetes. 1983 Jan;32(1):61–66. doi: 10.2337/diab.32.1.61. [DOI] [PubMed] [Google Scholar]
  29. WADDELL W. J., BUTLER T. C. Calculation of intracellular pH from the distribution of 5,5-dimethyl-2,4-oxazolidinedione (DMO); application to skeletal muscle of the dog. J Clin Invest. 1959 May;38(5):720–729. doi: 10.1172/JCI103852. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES