Abstract
We studied the effects of vitamin A deficiency and repletion on rat insulin release and islet cellular retinol binding protein (CRBP) and cellular retinoic acid binding protein (CRABP). Biphasic insulin release from vitamin A-deficient perifused islets was markedly impaired. Release remained impaired with retinoic acid (RA) repletion, 2 micrograms/g diet compared to release from islets of rats repleted with retinol in the form of retinyl palmitate, 4 micrograms/g diet. Release normalized with RA, 8 micrograms/g diet. Vitamin A deficiency did not affect islet insulin content, cell size, number or structure. In vivo, vitamin A-deficient rats had impaired glucose-induced acute insulin release and glucose intolerance, which improved with repletion. Normal islets had greater concentrations of CRBP than CRABP; vitamin A deficiency reduced CRBP but not CRABP levels. We conclude retinol is required for normal insulin secretion. Retinoic acid may substitute for retinol in this function.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anzano M. A., Lamb A. J., Olson J. A. Growth, appetite, sequence of pathological signs and survival following the induction of rapid, synchronous vitamin A deficiency in the rat. J Nutr. 1979 Aug;109(8):1419–1431. doi: 10.1093/jn/109.8.1419. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Chertow B. S., Baker G. R. The effects of vitamin A on insulin release and glucose oxidation in isolated rat islets. Endocrinology. 1978 Nov;103(5):1562–1572. doi: 10.1210/endo-103-5-1562. [DOI] [PubMed] [Google Scholar]
- Chertow B. S., Baranetsky N. G., Sivitz W. I., Meda P., Webb M. D., Shih J. C. Cellular mechanisms of insulin release. Effects of retinoids on rat islet cell-to-cell adhesion, reaggregation, and insulin release. Diabetes. 1983 Jun;32(6):568–574. doi: 10.2337/diab.32.6.568. [DOI] [PubMed] [Google Scholar]
- Chertow B. S., Buschmann R. J., Kaplan R. L. Cellular mechanisms of insulin release. Effects of retinol on insulin release and islet ultrastructure. Diabetes. 1979 Aug;28(8):754–761. doi: 10.2337/diab.28.8.754. [DOI] [PubMed] [Google Scholar]
- Chertow B. S., Sivitz W. I., Baranetsky N. G., Clark S. A., Waite A., Deluca H. F. Cellular mechanisms of insulin release: the effects of vitamin D deficiency and repletion on rat insulin secretion. Endocrinology. 1983 Oct;113(4):1511–1518. doi: 10.1210/endo-113-4-1511. [DOI] [PubMed] [Google Scholar]
- Davies P. J., Murtaugh M. P., Moore W. T., Jr, Johnson G. S., Lucas D. Retinoic acid-induced expression of tissue transglutaminase in human promyelocytic leukemia (HL-60) cells. J Biol Chem. 1985 Apr 25;260(8):5166–5174. [PubMed] [Google Scholar]
- DeRuyter M. G., De Leenheer A. P. Simultaneous determination of retinol and retinyl esters in serum or plasma by reversed-phase high-performance liquid chromatography. Clin Chem. 1978 Nov;24(11):1920–1923. [PubMed] [Google Scholar]
- Eckert R. L., Green H. Cloning of cDNAs specifying vitamin A-responsive human keratins. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4321–4325. doi: 10.1073/pnas.81.14.4321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fuchs E., Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell. 1981 Sep;25(3):617–625. doi: 10.1016/0092-8674(81)90169-0. [DOI] [PubMed] [Google Scholar]
- Godfrey K. Statistics in practice. Comparing the means of several groups. N Engl J Med. 1985 Dec 5;313(23):1450–1456. doi: 10.1056/NEJM198512053132305. [DOI] [PubMed] [Google Scholar]
- Goodman D. S. Vitamin A and retinoids in health and disease. N Engl J Med. 1984 Apr 19;310(16):1023–1031. doi: 10.1056/NEJM198404193101605. [DOI] [PubMed] [Google Scholar]
- 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]
- Kato M., Blaner W. S., Mertz J. R., Das K., Kato K., Goodman D. S. Influence of retinoid nutritional status on cellular retinol- and cellular retinoic acid-binding protein concentrations in various rat tissues. J Biol Chem. 1985 Apr 25;260(8):4832–4838. [PubMed] [Google Scholar]
- Kato M., Kato K., Blaner W. S., Chertow B. S., Goodman D. S. Plasma and cellular retinoid-binding proteins and transthyretin (prealbumin) are all localized in the islets of Langerhans in the rat. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2488–2492. doi: 10.1073/pnas.82.8.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim K. H., Schwartz F., Fuchs E. Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4280–4284. doi: 10.1073/pnas.81.14.4280. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamb A. J., Apiwatanaporn P., Olson J. A. Induction of rapid, synchronous vitamin A deficiency in the rat. J Nutr. 1974 Sep;104(9):1140–1148. doi: 10.1093/jn/104.9.1140. [DOI] [PubMed] [Google Scholar]
- Lotan R. Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta. 1980 Mar 12;605(1):33–91. doi: 10.1016/0304-419x(80)90021-9. [DOI] [PubMed] [Google Scholar]
- Mordan L. J., Hui S. W., Bertram J. S. Modulation by retinyl acetate of microfilament bundle formation in C3H/10T1/2 cells. J Cell Biochem. 1984;24(1):15–25. doi: 10.1002/jcb.240240103. [DOI] [PubMed] [Google Scholar]
- Nakano K., Mizutani R. Increased sympathetic nervous system activity in rat spleen and heart following vitamin A depletion. J Nutr Sci Vitaminol (Tokyo) 1984 Apr;30(2):163–170. doi: 10.3177/jnsv.30.163. [DOI] [PubMed] [Google Scholar]
- Olson J. A., Rojanapo W., Lamb A. J. The effect of vitamin A status on the differentiation and function of goblet cells in the rat intestine. Ann N Y Acad Sci. 1981 Feb 27;359:181–191. doi: 10.1111/j.1749-6632.1981.tb12746.x. [DOI] [PubMed] [Google Scholar]
- Schubart U. K., Fields K. L. Identification of a calcium-regulated insulinoma cell phosphoprotein as an islet cell keratin. J Cell Biol. 1984 Mar;98(3):1001–1009. doi: 10.1083/jcb.98.3.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schubart U. K., Fleischer N., Erlichman J. Ca2+-dependent protein phosphorylation and insulin release in intact hamster insulinoma cells. Inhibition by trifluoperazine. J Biol Chem. 1980 Dec 10;255(23):11063–11066. [PubMed] [Google Scholar]
- Schubart U. K. Regulation of protein phosphorylation in hamster insulinoma cells. Identification of Ca2+-regulated cytoskeletal and cAMP-regulated cytosolic phosphoproteins by two-dimensional electrophoresis. J Biol Chem. 1982 Oct 25;257(20):12231–12238. [PubMed] [Google Scholar]
- Sener A., Dunlop M. E., Gomis R., Mathias P. C., Malaisse-Lagae F., Malaisse W. J. Role of transglutaminase in insulin release. Study with glycine and sarcosine methylesters. Endocrinology. 1985 Jul;117(1):237–242. doi: 10.1210/endo-117-1-237. [DOI] [PubMed] [Google Scholar]
- Suda T., DeLuca H. F., Tanaka Y. Biological activity of 25-hydroxyergocalciferol in rats. J Nutr. 1970 Sep;100(9):1049–1052. doi: 10.1093/jn/100.9.1049. [DOI] [PubMed] [Google Scholar]
- Thacher S. M., Coe E. L., Rice R. H. Retinoid suppression of transglutaminase activity and envelope competence in cultured human epidermal carcinoma cells. Hydrocortisone is a potent antagonist or retinyl acetate but not retinoic acid. Differentiation. 1985;29(1):82–87. doi: 10.1111/j.1432-0436.1985.tb00296.x. [DOI] [PubMed] [Google Scholar]
- WASHKO M. E., RICE E. W. Determination of glucose by an improved enzymatic procedure. Clin Chem. 1961 Oct;7:542–545. [PubMed] [Google Scholar]
- Wald G. The molecular basis of visual excitation. Nature. 1968 Aug 24;219(5156):800–807. doi: 10.1038/219800a0. [DOI] [PubMed] [Google Scholar]
- Wolf G. Multiple functions of vitamin A. Physiol Rev. 1984 Jul;64(3):873–937. doi: 10.1152/physrev.1984.64.3.873. [DOI] [PubMed] [Google Scholar]
- YALOW R. S., BERSON S. A. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960 Jul;39:1157–1175. doi: 10.1172/JCI104130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zawalich W. S., Dye E. S., Pagliara A. S., Rognstad R., Matschinsky F. M. Starvation diabetes in the rat: onset, recovery, and specificity of reduced responsiveness of pancreatic beta-cells. Endocrinology. 1979 May;104(5):1344–1351. doi: 10.1210/endo-104-5-1344. [DOI] [PubMed] [Google Scholar]