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. 1984 Mar;73(3):759–766. doi: 10.1172/JCI111269

Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas.

S Kadowaki, A W Norman
PMCID: PMC425078  PMID: 6323527

Abstract

We have reported previously that arginine-induced insulin secretion was impaired in the vitamin D-deficient rat pancreas, and that it was improved by dietary vitamin D repletion (Norman, A. W., B. J. Frankel, A. M. Heldt, and G. M. Grodsky, 1980, Science [Wash. DC]. 209:823-825). In this study, we evaluate in the perfused rat pancreas system whether the effects of vitamin D and its metabolites on insulin secretion are direct in action on the pancreas and limited to the secretagogue arginine, or whether they are secondary to the hypocalcemia or reduced caloric and calcium intake associated with vitamin D deficiency. In an experiment where vitamin D-replete (+D) rats were pair-fed to D-deficient (-D) rats fed ad lib., the secretion of insulin in response to arginine infusion in the +D perfused rat pancreas was threefold higher than in the -D control. In a second experiment, the serum calcium level was elevated from the characteristic hypocalcemic level of -D rats (4.9 +/- 0.1 mg/dl) to a normal calcemic level (10.0 +/- 0.3 mg/dl) by feeding the rats a -D diet with dietary calcium levels ranging from 0.4 to 4%. In these -D rats, the pancreatic perfusion study with the secretagogue arginine showed a similar blunted insulin secretion response in all groups in spite of the significant differences of serum calcium levels. In a third experiment, insulin secretion in response to the separate administration of arginine (10 mM), glucose (16.9 mM), and tolbutamide (0.37 mM) was found to be significantly higher in pair-fed, normocalcemic +D rats than in -D rats with normal calcium levels. These results indicate that vitamin D or its metabolites are essential for normal insulin secretion and that the dietary intake of calcium and the resulting serum calcium levels play a lesser role than vitamin D availability in mediating insulin secretion.

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Selected References

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  1. Arnold B. M., Kuttner M., Willis D. M., Hitchman A. J., Harrison J. E., Murray T. M. Radioimmunoassay studies of intestinal calcium-binding protein in the pig. II. The distribution of intestinal CaBP in pig tissues. Can J Physiol Pharmacol. 1975 Dec;53(6):1135–1140. doi: 10.1139/y75-158. [DOI] [PubMed] [Google Scholar]
  2. Ashcroft S. J. The control of insulin release by sugars. Ciba Found Symp. 1976;41:117–139. doi: 10.1002/9780470720233.ch7. [DOI] [PubMed] [Google Scholar]
  3. Best L., Malaisse W. J. Phosphatidylinositol and phosphatidic acid metabolism in rat pancreatic islets in response to neurotransmitter and hormonal stimuli. Biochim Biophys Acta. 1983 Jan 7;750(1):157–163. doi: 10.1016/0005-2760(83)90215-1. [DOI] [PubMed] [Google Scholar]
  4. Burr F. A., Burr B. Three mutations in Zea mays affecting zein accumulation: a comparison of zein polypeptides, in vitro synthesis and processing, mRNA levels, and genomic organization. J Cell Biol. 1982 Jul;94(1):201–206. doi: 10.1083/jcb.94.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cahill G. F., Jr, Herrera M. G., Morgan A. P., Soeldner J. S., Steinke J., Levy P. L., Reichard G. A., Jr, Kipnis D. M. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. doi: 10.1172/JCI105481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Christakos S., Friedlander E. J., Frandsen B. R., Norman A. W. Studies on the mode of action of calciferol. XIII. Development of a radioimmunoassay for vitamin D-dependent chick intestinal calcium-binding protein and tissue distribution. Endocrinology. 1979 May;104(5):1495–1503. doi: 10.1210/endo-104-5-1495. [DOI] [PubMed] [Google Scholar]
  7. Christakos S., Norman A. W. Studies on the mode of action of calciferol. XXIX. Biochemical characterization of 1,25-dihydroxyvitamin D3 receptors in chick pancreas and kidney cytosol. Endocrinology. 1981 Jan;108(1):140–149. doi: 10.1210/endo-108-1-140. [DOI] [PubMed] [Google Scholar]
  8. Clark S. A., Stumpf W. E., Sar M. Effect of 1,25 dihydroxyvitamin D3 on insulin secretion. Diabetes. 1981 May;30(5):382–386. doi: 10.2337/diab.30.5.382. [DOI] [PubMed] [Google Scholar]
  9. Douglas W. W. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol. 1968 Nov;34(3):451–474. doi: 10.1111/j.1476-5381.1968.tb08474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GRODSKY G. M., BATTS A. A., BENNETT L. L., VCELLA C., MCWILLIAMS N. B., SMITH D. F. EFFECTS OF CARBOHYDRATES ON SECRETION OF INSULIN FROM ISOLATED RAT PANCREAS. Am J Physiol. 1963 Oct;205:638–644. doi: 10.1152/ajplegacy.1963.205.4.638. [DOI] [PubMed] [Google Scholar]
  11. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  12. Kadowaki S., Taminato T., Chiba T., Mori K., Abe H., Goto Y., Seino Y., Matsukura S., Nozawa M., Fujita T. Somatostatin release from isolated perfused rat pancreas. Possible role of endogenous somatostatin on insulin release. Diabetes. 1979 Jun;28(6):600–603. doi: 10.2337/diab.28.6.600. [DOI] [PubMed] [Google Scholar]
  13. Kikuchi M., Wollheim C. B., Siegel E. G., Renold A. E., Sharp G. W. Biphasic insulin release in rat islets of Langerhans and the role of Intracellular Ca++ stores. Endocrinology. 1979 Oct;105(4):1013–1019. doi: 10.1210/endo-105-4-1013. [DOI] [PubMed] [Google Scholar]
  14. Malaisse W. J., Malaisse-Lagae F., Wright P. H. Effect of fasting upon insulin secretion in the rat. Am J Physiol. 1967 Oct;213(4):843–848. doi: 10.1152/ajplegacy.1967.213.4.843. [DOI] [PubMed] [Google Scholar]
  15. Matschinsky F. M., Rujanavech C., Pagliara A., Norfleet W. T. Adaptations of alpha2- and beta-cells of rat and mouse pancreatic islets to starvation, to refeeding after starvation, and to obesity. J Clin Invest. 1980 Jan;65(1):207–218. doi: 10.1172/JCI109652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morrissey R. L., Bucci T. J., Richard B., Empson N., Lufkin E. G. Calcium-binding protein: its cellular localization in jejunum, kidney and pancreas. Proc Soc Exp Biol Med. 1975 May;149(1):56–60. doi: 10.3181/00379727-149-38742. [DOI] [PubMed] [Google Scholar]
  17. Nemere I., Norman A. W. Vitamin D and intestinal cell membranes. Biochim Biophys Acta. 1982 Nov 30;694(3):307–327. doi: 10.1016/0304-4157(82)90010-7. [DOI] [PubMed] [Google Scholar]
  18. Norman A. W., Frankel J. B., Heldt A. M., Grodsky G. M. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science. 1980 Aug 15;209(4458):823–825. doi: 10.1126/science.6250216. [DOI] [PubMed] [Google Scholar]
  19. Norman A. W., Roth J., Orci L. The vitamin D endocrine system: steroid metabolism, hormone receptors, and biological response (calcium binding proteins). Endocr Rev. 1982 Fall;3(4):331–366. doi: 10.1210/edrv-3-4-331. [DOI] [PubMed] [Google Scholar]
  20. Pike J. W., Goozé L. L., Haussler M. R. Biochemical evidence for 1,25-dihydroxyvitamin D receptor macromolecules in parathyroid, pancreatic, pituitary, and placental tissues. Life Sci. 1980 Feb 4;26(5):407–414. doi: 10.1016/0024-3205(80)90158-7. [DOI] [PubMed] [Google Scholar]
  21. Pike J. W. Receptors for 1,25-dihydroxyvitamin D3 in chick pancreas: a partial physical and functional characterization. J Steroid Biochem. 1982 Mar;16(3):385–395. doi: 10.1016/0022-4731(82)90050-4. [DOI] [PubMed] [Google Scholar]
  22. RAABO E., TERKILDSEN T. C. On the enzymatic determination of blood glucose. Scand J Clin Lab Invest. 1960;12(4):402–407. doi: 10.3109/00365516009065404. [DOI] [PubMed] [Google Scholar]
  23. 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. 1975 Jul;7(4):287–290. doi: 10.1055/s-0028-1093756. [DOI] [PubMed] [Google Scholar]
  24. Roth J., Bonner-Weir S., Norman A. W., Orci L. Immunocytochemistry of vitamin D-dependent calcium binding protein in chick pancreas: exclusive localization. Endocrinology. 1982 Jun;110(6):2216–2218. doi: 10.1210/endo-110-6-2216. [DOI] [PubMed] [Google Scholar]
  25. STEENBOCK H., HERTING D. C. Vitamin D and growth. J Nutr. 1955 Dec 10;57(4):449–468. doi: 10.1093/jn/57.4.449. [DOI] [PubMed] [Google Scholar]
  26. Vance J. E., Buchanan K. D., Williams R. H. Effect of starvation and refeeding on serum immunoreactive glucagon and insulin levels. J Lab Clin Med. 1968 Aug;72(2):290–297. [PubMed] [Google Scholar]
  27. Wollheim C. B., Kikuchi M., Renold A. E., Sharp G. W. The roles of intracellular and extracellular Ca++ in glucose-stimulated biphasic insulin release by rat islets. J Clin Invest. 1978 Aug;62(2):451–458. doi: 10.1172/JCI109146. [DOI] [PMC free article] [PubMed] [Google Scholar]

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