Insulin resistance (IR), IR treated with vitamin D, IR treated with 1α-hydroxyvitamin D (1α-(OH)D), type 2 diabetes mellitus (T2DM), T2DM treated with vitamin D and T2DM treated with 1a-(OH)D were studied in animal models using aged Wistar rats. Glucose infusion rates and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D) and 1, 25-dihydroxyvitamin D (1, 25-(OH)2D) were measured. T2DM rats had higher UA than IR or normal rats, and levels of 25-(OH)D in all models were similar. IR rats had higher 1, 25-(OH)2D levels than T2DM rats, and had lower 1, 25-(OH)2D levels than normal rats. Treating IR or T2DM rats with vitamin D had no effect on 25-(OH)D or 1, 25-(OH)2D. Administration of 1α-(OH)D significantly increased 1, 25-(OH)2D in IR rats to above-normal levels, and significantly increased 1, 25-(OH)2D in T2DM rats to normal levels. In IR or T2DM, abnormal vitamin D metabolism is characterized by 1, 25-(OH)2D deficiency and is related to renal injury.
TakeyamaKKitanakaSSatoT: 25-Hydroxyvitamin D3 1α-hydroxylase and vitamin D synthesis. Science1997; 277: 1827–1830.
2.
OhyamaYYamasakiT: Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci2004; 9: 3007–3018.
3.
BlandRZehnderDHewisonM: Expression of 25-hydroxyvitamin D3–1α-hydroxylase along the nephron: New insights into renal vitamin D metabolism. Curr Opin Nephrol Hypertens2000; 9: 17–22.
4.
AndressDL: Vitamin D in chronic kidney disease: A systemic role for selective vitamin D receptor activation. Kidney Int2006; 69: 33–43.
5.
DussoASBrownAJSlatopolskyE: Vitamin D. Am J Physiol Renal Physiol2005; 289: F8–F28.
6.
MillerWLPortaleAA: Vitamin D biosynthesis and vitamin D 1 alpha-hydroxylase deficiency. Endocr Dev2003; 6: 156–174.
7.
ParvanovaAITrevisanRIlievIP: Insulin resistance and microalbuminuria: A cross-sectional, case-control study of 158 patients with type 2 diabetes and different degrees of urinary albumin excretion. Diabetes2006; 55: 1456–1562.
8.
KawanoKHirashimaTMoriS: Spontaneous long-term hyperglycemic rat with diabetic complications: Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes1992; 41: 1422–1428.
9.
BaderRBaderHGrundKE: Structure and function of the kidney in diabetic glomerulosclerosis: Correlations between morphological and functional parameters. Pathol Res Pract1980; 167: 204–216.
10.
GilbertRECooperME: The tubulointerstitium in progressive diabetic kidney disease: More than an aftermath of glomerular injury?Kidney Int1999; 56: 1627–1637.
11.
NathKA: The tubulointerstitium in progressive renal disease. Kidney Int1998; 54: 992–994.
12.
NathKA: Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis1992; 20: 1–17.
13.
OrtizAZiyadehFNNeilsonEG: Expression of apoptosis-regulatory genes in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys. J Invest Med1997; 45: 50–56.
14.
WolfG: Cell cycle regulation in diabetic nephropathy. Kidney Int Suppl2000; 77: S59–S66.
15.
ZiyadehFN: Significance of tubulointerstitial changes in diabetic renal disease. Kidney Int Suppl1996; 54: S10–S13.
16.
EddyA: Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol1996; 7: 2495–2508.
CooperME: Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet1998; 352: 213–219.
19.
YaqoobMMcClellandPPatrickAW: Tubulopathy with macroalbuminuria due to diabetic nephropathy and primary glomerulonephritis. Kidney Int Suppl1994; 47: S101–S104.
20.
YaqoobMMcClellandPPatrickAW: Evidence of oxidant injury and tubular damage in early diabetic nephropathy. QJM1994; 87: 601–607.
JonesSCSaundersHJPollockCA: High glucose increases growth and collagen synthesis in cultured human tubulointerstitial cells. Diabet Med1999; 16: 932–938.
23.
UenoMKawashimaSNishiS: Tubulointerstitial lesions in non-insulin dependent diabetes mellitus. Kidney Int Suppl1997; 63: S191–S194.
24.
MarcussenN: Atubular glomeruli and the structural basis for chronic renal failure. Lab Invest1992; 66: 265–284.
25.
HolmJHemmingsenLNielsenNV: Low-molecular-mass proteinuria as a marker of proximal renal tubular dysfunction in normo-and microalbuminuric non-insulin-dependent diabetic subjects. Clin Chem1993; 39: 517–519.
26.
HongCYChiaKS: Markers of diabetic nephropathy. J Diabetes Complications1998; 12: 43–60.
27.
NuytsGDYaqoobMNouwenEJ: Human urinary intestinal alkaline phosphatase as an indicator of S3-segment-specific alterations in incipient diabetic nephropathy. Nephrol Dial Transplant1994; 9: 377–381.
28.
PfleidererSZimmerhacklLBKinneR: Renal proximal and distal tubular function is attenuated in diabetes mellitus type 1 as determined by the renal excretion of alpha 1-microglobulin and Tamm-Horsfall protein. Clin Investig1993; 71: 972–977.
29.
BoucherBJ: Hypovitaminosis D and risk of type 2 diabetes in British South Asians. Diabet Med2006; 23: 336.
30.
MathieuCGysemansCGiuliettiA: Vitamin D and diabetes. Diabetologia2005; 48: 1247–1257.
31.
PietschmannPSchernthanerGWoloszczukW: Serum osteocalcin levels in diabetes mellitus: Analysis of the type of diabetes and microvascular complications. Diabetologia1988; 31: 892–895.
32.
RosenbaumMLeibelRLHirschJ: Obesity. N Engl J Med1997; 337: 396–407.
33.
PittasAGDawson-HughesBLiT: Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care2006; 29: 650–656.
34.
BorissovaAMTankovaTKirilovG: The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract2003; 57: 258–261.
35.
ThrailkillKMLumpkinCKJrBunnRC: Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab2005; 289: E735–E745.
36.
CamastraSMancoMMariA: Beta-cell function in morbidly obese subjects during free living: Long-term effects of weight loss. Diabetes2005; 54: 2382–2389.
37.
TiikkainenMTamminenMHakkinenAM: Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes. Obes Res2002; 10: 859–867.
38.
De CosmoSMinennaALudovicoO: Increased urinary albumin excretion, insulin resistance and related cardiovascular risk factors in patients with type 2 diabetes: Evidence of a sex-specific association. Diabetes Care2005; 28: 910–915.
39.
HoehnerCMGreenlundKJNajarianS Rith: Association of the insulin resistance syndrome and microalbuminuria among nondiabetic native Americans. The Inter-Tribal Heart Project. J Am Soc Nephrol2002; 13: 1626–1634.
