Abstract
1. The effect of hydrochlorothiazide on insulin release, 36Cl- fluxes and 45Ca2+ uptake was tested in beta-cell-rich mouse pancreatic islets. 2. At high glucose concentrations (10 and 20 mmol l-1), low concentrations of hydrochlorothiazide (0.1-1.0 mumol l-1) reduced insulin release by 22-42%. At lower glucose concentrations (3-8.5 mmol l-1) insulin release was not affected by the drug. 3. Neither short-term influx (3 min) nor net accumulation (60 min) of 36Cl- in the islets was affected by hydrochlorothiazide (0.1-500 mumol l-1). 4. Glucose-stimulated 45Ca2+ uptake was significantly reduced by hydrochlorothiazide (1-10 mumol l-1). 5. The data suggest that the diabetogenic effect of hydrochlorothiazide, at least in part, can be mediated by direct inhibition of insulin release from the pancreatic beta-cells. The inhibition is not mediated by reduced chloride fluxes but may rather be caused by inhibition of calcium uptake.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amery A., Berthaux P., Bulpitt C., Deruyttere M., de Schaepdryver A., Dollery C., Fagard R., Forette F., Hellemans J., Lund-Johansen P. Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly. Lancet. 1978 Apr 1;1(8066):681–683. doi: 10.1016/s0140-6736(78)90797-3. [DOI] [PubMed] [Google Scholar]
- Beermann B., Groschinsky-grind M. Antihypertensive effect of various doses of hydrochlorothiazide and its relation to the plasma level of the drug. Eur J Clin Pharmacol. 1978 May 31;13(3):195–201. doi: 10.1007/BF00609982. [DOI] [PubMed] [Google Scholar]
- Brass E. P. Effects of antihypertensive drugs on endocrine function. Drugs. 1984 May;27(5):447–458. doi: 10.2165/00003495-198427050-00004. [DOI] [PubMed] [Google Scholar]
- Furman B. L. Impairment of glucose tolerance produced by diuretics and other drugs. Pharmacol Ther. 1981;12(3):613–649. doi: 10.1016/0163-7258(81)90102-9. [DOI] [PubMed] [Google Scholar]
- GOLDNER M. G., ZAROWITZ H., AKGUN S. Hyperglycemia and glycosuria due to thiazide derivatives administered in diabetes mellitus. N Engl J Med. 1960 Feb 25;262:403–405. doi: 10.1056/NEJM196002252620807. [DOI] [PubMed] [Google Scholar]
- Hahn H. J., Hellman B., Lernmark A., Sehlin J., Täljedal I. B. The pancreatic beta-cell recognition of insulin secretogogues. Influence of neuraminidase treatment on the release of insulin and the islet content of insulin, sialic acid, and cyclic adenosine 3':5'-monophosphate. J Biol Chem. 1974 Aug 25;249(16):5275–5284. [PubMed] [Google Scholar]
- Helderman J. H., Elahi D., Andersen D. K., Raizes G. S., Tobin J. D., Shocken D., Andres R. Prevention of the glucose intolerance of thiazide diuretics by maintenance of body potassium. Diabetes. 1983 Feb;32(2):106–111. doi: 10.2337/diab.32.2.106. [DOI] [PubMed] [Google Scholar]
- Hellman B., Idahl L. A., Lernmark A., Sehlin J., Täljedal I. B. The pancreatic beta-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release. Biochem J. 1974 Jan;138(1):33–45. doi: 10.1042/bj1380033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hellman B., Sehlin J., Täljedal I. B. Effects of glucose on 45Ca2+ uptake by pancreatic islets as studied with the lanthanum method. J Physiol. 1976 Jan;254(3):639–656. doi: 10.1113/jphysiol.1976.sp011250. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Henquin J. C., Meissner H. P. Opposite effects of tolbutamide and diazoxide on 86Rb+ fluxes and membrane potential in pancreatic B cells. Biochem Pharmacol. 1982 Apr 1;31(7):1407–1415. doi: 10.1016/0006-2952(82)90036-3. [DOI] [PubMed] [Google Scholar]
- Hermansen K., Schmitz O., Mogensen C. E. Effects of a thiazide diuretic (hydroflumethiazide) and a loop diuretic (bumetanide) on the endocrine pancreas: studies in vitro. Metabolism. 1985 Aug;34(8):784–789. doi: 10.1016/0026-0495(85)90031-9. [DOI] [PubMed] [Google Scholar]
- Lindström P., Norlund L., Sandstöm P. E., Sehlin J. Evidence for co-transport of sodium, potassium and chloride in mouse pancreatic islets. J Physiol. 1988 Jun;400:223–236. doi: 10.1113/jphysiol.1988.sp017118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malaisse W., Malaisse-Legae F. Effect of thiazides upon insulin secretion in vitro. Arch Int Pharmacodyn Ther. 1968 Jan;171(1):235–239. [PubMed] [Google Scholar]
- Petersen O. H., Findlay I. Electrophysiology of the pancreas. Physiol Rev. 1987 Jul;67(3):1054–1116. doi: 10.1152/physrev.1987.67.3.1054. [DOI] [PubMed] [Google Scholar]
- Sandström P. E. Bumetanide reduces insulin release by a direct effect on the pancreatic beta-cells. Eur J Pharmacol. 1990 Oct 23;187(3):377–383. doi: 10.1016/0014-2999(90)90365-d. [DOI] [PubMed] [Google Scholar]
- Sandström P. E., Sehlin J. Furosemide-induced glucose intolerance in mice is associated with reduced insulin secretion. Eur J Pharmacol. 1988 Mar 15;147(3):403–409. doi: 10.1016/0014-2999(88)90175-6. [DOI] [PubMed] [Google Scholar]
- Sandström P. E., Sehlin J. Na+ participates in loop diuretic-sensitive Cl(-)-cation co-transport in the pancreatic beta-cells. Biochim Biophys Acta. 1990 Apr 13;1023(2):191–196. doi: 10.1016/0005-2736(90)90413-i. [DOI] [PubMed] [Google Scholar]
- Sehlin J. Are Cl- mechanisms in mouse pancreatic islets involved in insulin release? Ups J Med Sci. 1981;86(2):177–182. doi: 10.3109/03009738109179226. [DOI] [PubMed] [Google Scholar]
- Stokes J. B. Sodium chloride absorption by the urinary bladder of the winter flounder. A thiazide-sensitive, electrically neutral transport system. J Clin Invest. 1984 Jul;74(1):7–16. doi: 10.1172/JCI111420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trube G., Rorsman P., Ohno-Shosaku T. Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells. Pflugers Arch. 1986 Nov;407(5):493–499. doi: 10.1007/BF00657506. [DOI] [PubMed] [Google Scholar]
- WILKINS R. W. New drugs for the treatment of hypertension. Ann Intern Med. 1959 Jan;50(1):1–10. doi: 10.7326/0003-4819-50-1-1. [DOI] [PubMed] [Google Scholar]
- Wollheim C. B., Sharp G. W. Regulation of insulin release by calcium. Physiol Rev. 1981 Oct;61(4):914–973. doi: 10.1152/physrev.1981.61.4.914. [DOI] [PubMed] [Google Scholar]