PMID- 19542734
OWN - NLM
STAT- MEDLINE
DCOM- 20090902
LR  - 20211020
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Linking)
VI  - 32
IP  - 3
DP  - 2009 Mar
TI  - The relationship among renal injury, changed activity of renal 1-alpha 
      hydroxylase and bone loss in elderly rats with insulin resistance or Type 2 
      diabetes mellitus.
PG  - 196-201
AB  - BACKGROUND AND OBJECTIVE: Chronic kidney disease can lead to a decrease in active 
      vitamin D [1,25-(OH)2D], which may be reversed by 1-alpha hydroxyvitamin D 
      [1-alpha(OH)D]. Renal 1-alpha hydroxylase, expressed in renal tubular epithelial 
      cells, is a key enzyme in the synthesis of 1,25-(OH)2D. 1,25- (OH)2D plays an 
      important role in the regulation of calcium and phosphate metabolism, and its 
      deficiency can result in osteoporosis. Type 2 diabetes mellitus (T2DM) and 
      insulin resistance (IR) are associated with renal injury, decrease in 1,25-(OH)2D 
      and bone loss. The study aimed to explore the relationship among renal injury, 
      decrease in 1,25-(OH)2D and bone loss in the presence of IR or T2DM, as well as 
      the role of renal 1-alpha hydroxylase in the process. MATERIALS AND METHODS: 
      Fifty 18-month-old male Wistar rats were randomized into 5 groups: normal control 
      group (Group N), IR group (Group I), T2DM group (Group D), No.1 treatment group 
      (Group T1), and No.2 treatment group (Group T2), 10 in each group. High-fat diet 
      was administered to induce IR, while high-fat diet and low-dose streptozotocin 
      were jointly applied to induce T2DM. Rats in Groups T1 and T2 were treated with 
      vitamin D and 1-alpha(OH)D, respectively. At week 12, IR was determined by the 
      use of euglycemic insulin clamp technique for rats in each group, and then 
      glucose infusion rate (GIR) was calculated. Meanwhile, urinary albumin (UA), 
      serum 25-(OH)D and 1,25-(OH)2D levels were determined by radioimmunoassay. After 
      the rats were sacrificed, bone mineral density (BMD) in femoral bone and lumbar 
      vertebrae was measured by the use of dual energy X-ray absorption. RESULTS: The 
      GIR in Group N was significantly higher than that of the other 4 groups (p<0.01). 
      Compared with Groups N (p<0.01) or I (p<0.05), the UA levels in Groups D, T1, and 
      T2 were obviously higher. The UA level in Group I was higher than that of Group 
      N, but the difference was not significant (p>0.05). In Groups D and I, the UA 
      levels showed a negative correlation with GIR. No significant difference was 
      observed in the levels of 25-hydroxyvitamin D [25-(OH)D]. The levels of 
      1,25-(OH)2D in Groups D and T1 were markedly lower than that of Groups N or T2 
      (p<0.01). The 1,25-(OH)2D level in Group I was lower than that of Group N 
      (p<0.05), but higher than that of Group D (p<0.01). The 1,25-(OH)2D level in 
      Group T2 was nearly equivalent to that of Group N. In Groups D and I, the levels 
      of 1,25-(OH)2D were negatively correlated with UA, and positively correlated with 
      GIR. The BMD levels in lumbar vertebrae or femoral bone in Groups D and T1 were 
      similar, but both were lower than that of Groups T2 (p<0.05) and N (p<0.01). The 
      BMD levels were lower in Groups I and T2 compared with that of Group N (p<0.05), 
      but higher than that of Groups D and T1 (p<0.05). The BMD levels in lumbar 
      vertebrae or femoral bone in Groups I and D were positively correlated with GIR. 
      The BMD level in lumbar vertebrae or femoral bone in Group D showed negative 
      correlation with UA. CONCLUSION: In elderly rats with T2DM or IR, renal injury 
      may cause decreased activity of renal 1-alpha hydroxylase, which may result in 
      bone loss and disturbance in VD metabolism, mainly manifesting as a significant 
      reduction in the 1,25-(OH)2D level.
FAU - Huang, C-Q
AU  - Huang CQ
AD  - Department of Geriatrics, The Third Hospital of Mianyang, Mianyang, PR China. 
      huangshan319@yahoo.com.cn
FAU - Ma, G-Z
AU  - Ma GZ
FAU - Tao, M-D
AU  - Tao MD
FAU - Ma, X-L
AU  - Ma XL
FAU - Liu, Q-X
AU  - Liu QX
FAU - Feng, J
AU  - Feng J
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - 0 (Blood Glucose)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 1.14.15.18 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase)
RN  - FXC9231JVH (Calcitriol)
RN  - P6YZ13C99Q (Calcifediol)
SB  - IM
MH  - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*metabolism
MH  - Aging/metabolism/physiology
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Bone Density/physiology
MH  - Calcifediol/blood
MH  - Calcitriol/blood
MH  - Diabetes Mellitus, Experimental/blood/complications/metabolism
MH  - Diabetes Mellitus, Type 2/blood/*complications/metabolism
MH  - *Insulin Resistance/physiology
MH  - Kidney/enzymology
MH  - Male
MH  - Osteoporosis/blood/*etiology/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Renal Insufficiency, Chronic/blood/*complications/metabolism
MH  - Streptozocin
MH  - Vitamin D Deficiency/etiology/metabolism
EDAT- 2009/06/23 09:00
MHDA- 2009/09/03 06:00
CRDT- 2009/06/23 09:00
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/09/03 06:00 [medline]
AID - 6336 [pii]
AID - 10.1007/BF03346452 [doi]
PST - ppublish
SO  - J Endocrinol Invest. 2009 Mar;32(3):196-201. doi: 10.1007/BF03346452.