Lack of Effect of Vitamin D Administration during Pregnancy and Early Life on Diabetes Incidence in the Non-obese Diabetic Mouse

M. I. Hawa; M. G. Valorani; L. R. Buckley; P. E. Beales; A. Afeltra; F. Cacciapaglia; R. D. G. Leslie; P. Pozzilli

doi:10.1055/s-2004-825926

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2004; 36(9): 620-624
DOI: 10.1055/s-2004-825926

Original Clinical

Lack of Effect of Vitamin D Administration during Pregnancy and Early Life on Diabetes Incidence in the Non-obese Diabetic Mouse

M. I. Hawa¹ , M. G. Valorani¹ , L. R. Buckley¹ , P. E. Beales¹ , A. Afeltra² , F. Cacciapaglia² , R. D. G. Leslie¹ , P. Pozzilli^1, ²

¹Department of Diabetes, Institute of Cell and Molecular Science, Barts and the London, Queen Mary, University of London UK
²Departments of Endocrinology and Immunology, University Campus Bio-Medico, Rome, Italy

Abstract

Background and aims: Several studies have suggested that vitamin D supplementation in early life may reduce the risk of developing type 1 diabetes in later life. The non-obese diabetic (NOD) mouse is a model of spontaneous type 1 diabetes currently used for testing hypothesis/compounds aimed at disease prevention. In this study, we tested the effect of vitamin D (16 IU by gavage) on diabetes incidence in NOD/Ba mice treated from conception with olive oil containing vitamin D via maternal dosing up to 10 weeks of age and followed up until 32 weeks of age.

Methods: Twelve breeding pairs were administered olive oil containing vitamin D during pregnancy, 15 days following the birth of the pups and for the next 10 weeks subsequently. The same breeding pairs were bred again after a clearance period of 15 days using a control solution to produce a control litter. This control group received a control solution for the same period of time. Diabetes incidence, degree of insulitis, and insulin content in the pancreas were investigated in the two groups.

Results: 12 vitamin D-treated NOD mice developed diabetes compared to 15 animals in the control group (Log rank test p = 0.899, NS). There were no significant differences between the groups in diabetes incidence, time of onset of the disease, degree of insulitis, or the insulin content in the pancreas.

Conclusion: Vitamin D administered in utero and in the early stages of life at the dosage used does not change the incidence of diabetes or modify the disease process that leads to beta cell destruction in the NOD mouse.

Key words

NOD mouse · Vitamin D · 1,25-(OH)₂D₃ · Type 1 diabetes · Insulitis · Immunointervention

Full Text

References

1 Pozzilli P, Signore A, Williams A J, Beales P E. NOD mouse colonies around the world, recent facts and figures. Immunol Today. 1993; 14 193-196
2 Olmos P, A’Hern R, Heaton D A, Millward B A, Risley D, Pyke D A, Leslie R DG. The significance of the concordance rate for type 1 (insulin dependent) diabetes in identical twins. Diabetologia. 1988; 31 747-750
3 Akerblom H K, Vaarala O, Hyoty H, Ilonen J, Knip M. Environmental Factors in the etiology of type 1 diabetes. Am J Med Genetics. 2002; 115 18-29
4 Kolb H, Pozzilli P. Cow's milk and type 1 diabetes: the gut immune system deserves attention. Immunol Today. 1999; 20 108-110
5 Beales P E, Elliott R B, Flohe S, Hill J P, Kolb H, Pozzilli P, Wang G S, Wasmuth H, Scott F W. A multi-centre, blinded international trial of the effect of A (1) and A (2) beta - casein variants on diabetes incidence in two rodent models of spontaneous type 1 diabetes. Diabetologia. 2002; 45 1240-1246
6 Beales P E, Burr L A, Webb G P, Mansfield K J, Pozzilli P. Diet can influence the ability of nicotinamide to prevent diabetes in the non obese diabetic mouse: a preliminary study. Diab Metab Res Rev. 1999; 15 21-28
7 Kolb H, Pozzilli P. Cow's milk and type 1 diabetes: the gut immune system deserves attention. Immunol Today. 1999; 20 108-110
8 Scott F W, Cloutier H E, Kleeman R, Woerz-Pagenstert U, Rowsell P, Modler H W, Lolb H. Potential mechanisms by which certain foods promote or inhibit the development of spontaneous diabetes in BB rats: dose, timing, early effect on islet area, and switch from Th1 to Th2 cells. Diabetes;. 1997; 46 589-598
9 Hypponen E, Laara E, Reunanen A, jarvelin M R, Virtanen S M. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358 1500-1103
10 Zella J B, McCary L C, DeLuca H. Oral Administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Arch Bioch & Bioph. 2003; 417 77-80
11 Casteels K M, Mathieu C, Waer M, Valckx D, Overbergh L, Laureys J M, Bouillon R C. Prevention of type I diabetes in non obese diabetic mice by late intervention with nonhypercalcemic analogues of 1,25-dihydroxyvitamin D3 in combination with a short induction course of cyclosporin A. Endocrinology. 1998; 139 95-102
12 Bruns M E, Bruns D E, Avioli L V. Vitamin D-dependent calcium-binding protein of rat intestine: changes during postnatal development and sensitivity to 1,25-dihydroxycholecalciferol. Endocrinology. 1979; 105 934-938
13 Akerblom H K, Knip M. Putative environmental factors in type 1 diabetes. Diabetes Metab Rev. 1998. Mar; 14 (1) 31-67
14 EURODIAB ACE Study Group . Variation and trends in incidence of childhood diabetes in Europe. Lancet. 2000; 355 873-876
15 Staples J A, Ponsonby A L, Lim L L, McMichael A J. Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence. Environ Health Perspect. 2003; 111 518-523
16 Leader S, Mallick R. Tapping the savings from vitamin-based prevention. Manag Care Interface. 1998; 11 95-99
17 Pozzilli P, Picardi A, Manfrini S. Cow's milk and trials for prevention of type 1 diabetes. Diabet Med. 2003; 20 871-872
18 Deluca H F, Cantorna M T. Vitamin D: its role and uses in immunology. FASEB J. 2001; 14 2579-2585
19 Bhalla A K, Amento E P, Clemens T L, Holick M F, Krane S M. Specific high-affinity receptors for 1,25 dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab. 1983; 57 1309-1310
20 Mathieu C, Adorini L. The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents. Trends Mol Med. 2002; 8 174-179
21 Cantorna M T. Vitamin D and Autoimmunity: Is vitamin D status an environmental factor affecting autoimmune disease prevalence?. Proc Soc Exp Biol Med. 2000; 223 230-233
22 Cantorna M T, Hayes C E, Deluca H F. 1,25-djhydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis. Proc Natl Acad Sci USA. 1996; 93 7861-7864
23 Gregori S, Giarratana N, Smoroldo S, Uskokovic M, Adorini L. A1,alph,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes. 2002; 51 367-1374
24 Cantoma M T, Munsick C, Bemiss C, Mhon B. 1 ,25 dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000; 11 2648-2652
25 Hayes C E, Nashold F E, Spach K M, Pedersen L B. The immunological functions of the vitamin D endocrine system. Cell Mol Biol. 2003; 49 277-300
26 Hahn H J, Kuttler B, Mathieu C, Bouillon R. 1,25-Dihydroxyvitamin D3 reduces MHC antigen expression on pancreatic beta cells in vitro. Transpl Proc. 1997; 29 2156-2157
27 van Etten E, Decallonne B, Mathieu C. 1,25-dihydroxycholecalciferol: endocrinology meets the immune system. Proc Nutr Soc. 2002; 61 375-380
28 Adorini L, Penna G, Giarratana N, Uskokovic M. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem. 2003; 88 227-233
29 Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999; 69 842-856

Prof. P. Pozzilli

Department of Diabetes, St. Bartholomew's Hospital

West Smithfield · London EC1A 7BE · UK

Phone: +44 (20) 76 01 74 52

Fax: +44 (20) 76 01 74 49

Email: p.p.pozzilli@qmul.ac.uk