scholarly journals Dysregulation of the Intrarenal Vitamin D Endocytic Pathway in a Nephropathy-Prone Mouse Model of Type 1 Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
John L. Fowlkes ◽  
R. Clay Bunn ◽  
Gael E. Cockrell ◽  
Lindsey M. Clark ◽  
Elizabeth C. Wahl ◽  
...  

Microalbuminuria in humans with Type 1 diabetes (T1D) is associated with increased urinary excretion of megalin, as well as many megalin ligands, including vitamin-D-binding protein (VDBP). We examined the DBA/2J diabetic mouse, nephropathy prone model, to determine if megalin and VDBP excretion coincide with the development of diabetic nephropathy. Megalin, VDBP, and 25-hydroxy-vitamin D (25-OHD) were measured in urine, and genes involved in vitamin D metabolism were assessed in renal tissues from diabetic and control mice at 10, 15, and 18 weeks following the onset of diabetes. Megalin, VDBP, and 25-OHD were increased in the urine of diabetic mice. 1-α hydroxylase (CYP27B1) mRNA in the kidney was persistently increased in diabetic mice, as were several vitamin D-target genes. These studies show that intrarenal vitamin D handling is altered in the diabetic kidney, and they suggest that in T1D, urinary losses of VDBP may portend risk for intrarenal and extrarenal vitamin D deficiencies.

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3873
Author(s):  
Alexandra Povaliaeva ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Viktor Bogdanov ◽  
Larisa Dzeranova ◽  
...  

In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a therapeutic dose. All patients received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. The studied groups had no significant differences in baseline parameters except that the patients with diabetes showed higher baseline levels of free 25(OH)D (p < 0.05). They also lacked a correlation between the measured and calculated free 25(OH)D in contrast to the patients from the control group (r = 0.41, p > 0.05 vs. r = 0.88, p < 0.05), possibly due to the glycosylation of binding proteins, which affects the affinity constant for 25(OH)D. The elevation of vitamin D levels after the administration of cholecalciferol was comparable in both groups, with slightly higher 25(OH)D3 levels observed in the diabetes group throughout the study since Day 1 (p < 0.05). Overall, our data indicate that in patients with adequately controlled T1DM 25(OH)D3 levels and the therapeutic response to cholecalciferol is similar to that in healthy individuals.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Daniel Dowling ◽  
Niamh Corrigan ◽  
Stephen Horgan ◽  
Chris J. Watson ◽  
John Baugh ◽  
...  

Purpose. To investigate cardiomyopathy in offspring in a mouse model of pregestational type 1 diabetic pregnancy.Methods. Pregestational diabetes was induced with STZ administration in female C57BL6/J mice that were subsequently mated with healthy C57BL6/J males. Offspring were sacrificed at embryonic day 18.5 and 6-week adolescent and 12-week adult stages. The size and number of cardiomyocyte nuclei and also the extent of collagen deposition within the hearts of diabetic and control offspring were assessed following cardiac tissue staining with either haematoxylin and eosin or Picrosirius red and subsequently quantified using automated digital image analysis.Results. Offspring from diabetic mice at embryonic day 18.5 had a significantly higher number of cardiomyocyte nuclei present compared to controls. These nuclei were also significantly smaller than controls. Collagen deposition was shown to be significantly increased in the hearts of diabetic offspring at the same age. No significant differences were found between the groups at 6 and 12 weeks.Conclusions. Our results from offspring of type 1 diabetic mice show increased myocardial collagen deposition in late gestation and have increased myocardial nuclear counts (hyperplasia) as opposed to increased myocardial nuclear size (hypertrophy) in late gestation. These changes normalize postpartum after removal from the maternal intrauterine environment.


2013 ◽  
Vol 15 (6) ◽  
pp. 416-421 ◽  
Author(s):  
Steffen U Thorsen ◽  
Henrik B Mortensen ◽  
Bendix Carstensen ◽  
Mogens Fenger ◽  
Betina H Thuesen ◽  
...  

Author(s):  
Yilin Hou ◽  
An Song ◽  
Yuxin Jin ◽  
Qiuyang Xia ◽  
Guangyao Song ◽  
...  

AbstractIt remains debatable whether vitamin D plays any role as a risk factor for type 1 diabetes mellitus (T1DM). We have summarized the effect of circulating 25-hydroxy vitamin D [25(OH)D] concentration on the risk of developing T1DM via a dose–response meta-analysis. We undertook a database search on PubMed, Embase, and Cochrane Library from inception to January 2020. A meta-analysis based on random-effects model was applied. Subgroup analysis and meta-regression were performed to inspect the source of heterogeneity. Dose–response data were examined using the generalized least squares trend estimation method. This study was registered with the PROSPERO (ID: CRD42020166174). In total, 16 studies including 10,605 participants (3913 case patients) were included. The pooled odds ratios (OR) and 95% confidence intervals (95% CI) for the highest versus the lowest 25(OH)D concentration was 0.39 (0.27, 0.57), with a high heterogeneity (I2 = 76.7%, P < 0.001). Meta-regression analysis identified latitude (P = 0.02), adjustment for gender (P = 0.001), and 25(OH)D stratification (P < 0.001) as sources of heterogeneity. Furthermore, the nonlinear dose–response analysis determined the OR (95% CI) of T1DM to be 0.91 (0.90, 0.93) per 10 nmol/L increase in the 25(OH)D concentration. A ‘U’-shaped association was found between serum 25(OH)D concentration and risk of T1DM. The present study highlights the significant inverse association between the circulating 25(OH)D concentration and the risk of T1DM.


Diabetologia ◽  
2004 ◽  
Vol 47 (3) ◽  
pp. 451-462 ◽  
Author(s):  
A. Giulietti ◽  
C. Gysemans ◽  
K. Stoffels ◽  
E. van Etten ◽  
B. Decallonne ◽  
...  

Diabetes ◽  
2007 ◽  
Vol 56 (10) ◽  
pp. 2616-2621 ◽  
Author(s):  
R. Bailey ◽  
J. D. Cooper ◽  
L. Zeitels ◽  
D. J. Smyth ◽  
J. H.M. Yang ◽  
...  

Diabetes ◽  
2011 ◽  
Vol 61 (1) ◽  
pp. 175-178 ◽  
Author(s):  
I. M. Sorensen ◽  
G. Joner ◽  
P. A. Jenum ◽  
A. Eskild ◽  
P. A. Torjesen ◽  
...  

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