Comments for:

1,25-Dihydroxyvitamin D₃ is a negative endocrine regulator of the renin-angiotensin system

Yan Chun Li, … , Shu Q. Liu, Li-Ping Cao

Yan Chun Li, … , Shu Q. Liu, Li-Ping Cao

Published July 15, 2002
Citation Information: J Clin Invest. 2002;110(2):229-238. https://doi.org/10.1172/JCI15219.

View: Text | PDF

Article

1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system: clue to the molecular basis of syndrome X.

Submitter: Hans Peter Rutz | hanspeter.rutz@psi.ch

Paul Scherrer Institute, Switzerland

Published August 20, 2002

In a brilliant piece of work, Li et al. have shown that the active metabolite of Vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol) is an important negative regulator of the renin-angiotensin system and hence, that calcitriol is required in sufficient amounts so as to facilitate maintenance of electrolyte balance, volume and moderate blood pressure (1).
Now, considering that: in obesity, the renin-angiotensin system is up -regulated (2,3); bioavailability of vitamin D3 (cholecalciferol) is reduced due to its deposition in body fat compartments, causing obesity- associated hypovitaminosis D (4); there is diabetes and a myriad of problems with global implications (5); that: in vitamin D-deficient rats (6-8), rabbits (9) and humans (10-13), there is impaired insulin secretion and glucose tolerance; that: calcitriol levels are inversely correlated to blood pressure, VLDL trigycerides, triglyceride removal, and insulin sensitivity (14); and considering that: after calcitriol administration, there is a stimulation of insulin secretion (15-17), a reversal of insulin resistance and hyperinsulinemia (18,19) and thus, a correction of glucose intolerance in vitamin D-deficiency; that: calcitriol corrects lipid abnormalities (20,21); and that: calcitriol is responsible for maintaining a balanced renin-angiotensin system and normal blood pressure (1), it is a rather obvious conclusion that hypovitaminosis D contributes to the development of the metabolic syndrome X (22,23), which thus is both treatable and preventable by appropriate supplementation of vitamin D, as has been suggested earlier based on preliminary data (14,24). Optimized recommendations for preventive and therapeutic substitution with cholecalciferol and/or calcitriol, and optimal target plasma levels for the various metabolites of vitamin D must now be worked out.
Hans Peter Rutz, hanspeter.rutz@psi.ch Division of Life Sciences, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland
References

1. Li, Y.C., Kong, J., Wei, M., Chen, Z.F., Liu, S.Q., Cao, L.P 2002. 1,25 -Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin- angiotensin system. J. Clin. Invest. 110:229-238.
2. Engeli, S., Sharma, A.M. 2001. The renin-angiotensin system and natriuretic peptides in obesity-associated hypertension. J. Mol. Med. 79:21-29.
3. Giacchetti, G., Faloia, E., Marinello, B., Sardu, C., Gatti, C., Camillino, M.A., Guerrieri, M., Mantero, F. 2002. Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. Am. J. Hypertens.15:381-388.
4. Wortsman, J., Matsuoka, L.Y., Chen, T.C., Lu, Z., Holik, F. 2000. Decreased bioavailability of vitamin D in obesity. Am. J. Clin. Nutr. 72:690-693.
5. Zimmet, P., Alberti, K.G.M.M., Shaw, J. 2001. Global and societal implications of the diabetes epidemic. Nature 414:782-787.
6. Cade, C., Norman, A.W. 1987. Rapid normalization/stimulation by 1,25- dihydroxyvitamin D3 of insulin secretion and glucose tolerance in the vitamin D-deficient rat. Endocrinology 120:1490-1497.
7. Beaulieu, C., Kestekian, R., Havrankova, J., Gascon-Barre, M. 1993. Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo. Diabetes 42:35-43.
8. Ayesha, I., Bala, T.S., Reddy, C.V., Raghuramulu, N. 2001. Vitamin D deficiency reduces insulin secretion and turnover in rats. Diabetes Nutr. Metab. 14:78-84.
9. Nyomby, B.L., Bouillon, R., De Moor, P. 1984. Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit. Endocrinology 115:191-197.
10. Mak, R.H. 1989. Insulin secretion in uremia: effect of parathyroid hormone and vitamin D metabolites. Kidney Int. Suppl. 27:S227-S230.
11. Mak, R.H. 1992. Intravenous 1,25 dihydroxycholecalciferol corrects glucose intolerance in hemodialysis patients. Kidney Int. 41:1049-1054.
12. Boucher, B.J., Mannan, N., Noonan, K., Hales, C.N., Evans, S.J. 1995. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia 38:1239-1245.
13. Bayes, K.C.R., Boucher, B.J., Feskens, E.J.M., Kromhout, D. 1997. Vitamin D, glucose tolerance and insulinaemia in elderly men. Diabetologia 40:344-347.
14. Lind, L., Hänni, A., Lithell, H., Hvarfner, A., Sörensen, O.H., Ljunghall, S. 1995. Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men. Am. J. Hypertens. 8:894- 901.
15. Kadowaki, S., Norman, A.W. 1985. Time course study of insulin secretion after 1,25dihydroxyvitamin D3 administration. Endocrinology 117:1765-1771.
16. Allegra, V., Luisetto, G., Mengozzi, G., Martimbianco, L., Vasile, A. 1994. Glucose-induced insulin secretion in uremia: role of 1 alpha,25(HO)2 -vitamin D3. Nephron 68:41-47.
17. Kumar, S., Davies, M., Zakaria, Y., Mawer, E.B., Gordon, C., Olukoga, A.O., Boulton, A.J. 1994. Postgrad. Med. J. 70:440-443.
18. Kautzky-Willer, A., Pacini, G., Barnas, U., Ludvik, B., Streli, C., Graf, H., Prager, R. 1995. Intravenous calcitriol normalizes insulin sensitivity in uremic patients. Kidney Int. 47:200-206.
19. Rudnicki, P.M., Molsted-Pedersen, L. 1997. Effect of 1,25- dihydroxycholecalciferol on glucose metabolism in gestational diabetes mellitus. Diabetologia 40:40-44.
20. Mak, R.H. 1998. 1,25-Dihydroxyvitamin D3 corrects insulin and lipid anomalities in uremia. Kidney Int. 53:1353-1357.
21. Khajehdehi, P. 2000. Effect of vitamins on the lipid profile of patients on regular hemodialysis. Scand. J. Urol. Nephrol. 34:62-66.
22. Lopez-Kandales, A. 2001. Metabolic syndrome X: a comprehensive review of the pathophysiology and recommended therapy. J. Med. 32:283-300.
23. Hauner, H. 2002. Insulin resistance and the metabolic syndrome – a challenge to the new millenium. Eur. J. Nutr. 56 Suppl 1:S25-S29.
24. Boucher, B.J. 1998. Inadequate vitamin D status: does it contribute to the disorders comprising syndrome 'X’? Br. J. Nutr. 79:315-237.