PMID- 31919470
OWN - NLM
STAT- MEDLINE
DCOM- 20201117
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jan 9
TI  - Excessive cholecalciferol supplementation increases kidney dysfunction associated 
      with intrarenal artery calcification in obese insulin-resistant mice.
PG  - 87
LID - 10.1038/s41598-019-55501-3 [doi]
LID - 87
AB  - Diabetes mellitus accelerates vascular calcification (VC) and increases the risk 
      of end-stage renal disease (ESRD). Nevertheless, the impact of VC in renal 
      disease progression in type 2 diabetes mellitus (T2DM) is poorly understood. We 
      addressed the effect of VC and mechanisms involved in renal dysfunction in a 
      murine model of insulin resistance and obesity (ob/ob), comparing with their 
      healthy littermates (C57BL/6). We analyzed VC and renal function in both mouse 
      strains after challenging them with Vitamin D(3) (VitD(3)). Although VitD(3) 
      similarly increased serum calcium and induced bone disease in both strains, 
      24-hour urine volume and creatinine pronouncedly decreased only in ob/ob mice. 
      Moreover, ob/ob increased urinary albumin/creatinine ratio (ACR), indicating 
      kidney dysfunction. In parallel, ob/ob developed extensive intrarenal VC after 
      VitD(3). Coincidently with increased intrarenal vascular mineralization, our 
      results demonstrated that Bone Morphogenetic Protein-2 (BMP-2) was highly 
      expressed in these arteries exclusively in ob/ob. These data depict a greater 
      susceptibility of ob/ob mice to develop renal disease after VitD(3) in comparison 
      to paired C57BL/6. In conclusion, this study unfolds novel mechanisms of 
      progressive renal dysfunction in diabetes mellitus (DM) after VitD(3) in vivo 
      associated with increased intrarenal VC and highlights possible harmful effects 
      of long-term supplementation of VitD(3) in this population.
FAU - Almeida, Youri E
AU  - Almeida YE
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Fessel, Melissa R
AU  - Fessel MR
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - do Carmo, Luciana Simao
AU  - do Carmo LS
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Jorgetti, Vanda
AU  - Jorgetti V
AD  - Department of Nephrology, Medical School, Universidade de Sao Paulo, Sao 
      Paulo/SP, 01246000, Brazil.
FAU - Farias-Silva, Elisangela
AU  - Farias-Silva E
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Pescatore, Luciana Alves
AU  - Pescatore LA
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
AD  - Laboratorio de Biologia Vascular, LIM-64, InCor, Hospital das Clinicas HCFMUSP, 
      Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo/SP, Brazil.
FAU - Gamarra, Lionel F
AU  - Gamarra LF
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Andrade, Maria Claudina
AU  - Andrade MC
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Simplicio-Filho, Antonio
AU  - Simplicio-Filho A
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Mangueira, Cristovao Luis Pitangueiras
AU  - Mangueira CLP
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Rangel, Erika B
AU  - Rangel EB
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil.
FAU - Liberman, Marcel
AU  - Liberman M
AUID- ORCID: 0000-0002-0040-1547
AD  - Hospital Israelita Albert Einstein, Sao Paulo/SP, 01425001, Brazil. 
      malib@einstein.br.
AD  - Laboratorio de Biologia Vascular, LIM-64, InCor, Hospital das Clinicas HCFMUSP, 
      Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo/SP, Brazil. 
      malib@einstein.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200109
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Calcium-Regulating Hormones and Agents)
RN  - 1C6V77QF41 (Cholecalciferol)
SB  - IM
MH  - Animals
MH  - Calcium-Regulating Hormones and Agents/pharmacology
MH  - Cholecalciferol/*pharmacology
MH  - Diabetes Mellitus, Experimental/*physiopathology
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - *Dietary Supplements
MH  - *Insulin Resistance
MH  - Kidney Diseases/etiology/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Obesity/physiopathology
MH  - Vascular Calcification/*complications
PMC - PMC6952360
COIS- The authors declare no competing interests.
EDAT- 2020/01/11 06:00
MHDA- 2020/11/18 06:00
PMCR- 2020/01/09
CRDT- 2020/01/11 06:00
PHST- 2019/04/11 00:00 [received]
PHST- 2019/11/29 00:00 [accepted]
PHST- 2020/01/11 06:00 [entrez]
PHST- 2020/01/11 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/01/09 00:00 [pmc-release]
AID - 10.1038/s41598-019-55501-3 [pii]
AID - 55501 [pii]
AID - 10.1038/s41598-019-55501-3 [doi]
PST - epublish
SO  - Sci Rep. 2020 Jan 9;10(1):87. doi: 10.1038/s41598-019-55501-3.