PMID- 23349674
OWN - NLM
STAT- MEDLINE
DCOM- 20130709
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic 
      beta-cells in humans: a pilot study of risk factors for T2DM.
PG  - e51642
LID - 10.1371/journal.pone.0051642 [doi]
LID - e51642
AB  - The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and 
      diverse environmental and genetic risk factors are well recognized. Single 
      nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a 
      protein involved in the secretion and action of insulin, and chronic exposure to 
      inorganic arsenic (iAs) through drinking water have been independently associated 
      with an increase in the risk for T2DM. In the present work we evaluated if 
      CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin 
      secretion (beta-cell function) and insulin sensitivity were evaluated indirectly 
      through validated indexes (HOMA2) in subjects with and without T2DM who have been 
      exposed to a gradient of iAs in their drinking water in northern Mexico. The 
      results were analyzed taking into account the presence of the risk factor SNPs 
      SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell 
      function and insulin sensitivity. An inverse association was found between 
      beta-cell function and iAs exposure, the association being more pronounced in 
      subjects with T2DM. Subjects without T2DM who were carriers of the at-risk 
      genotype SNP-43 or -44, also had significantly lower beta-cell function. The 
      association of SNP-43 with beta-cell function was dependent on iAs exposure, age, 
      gender and BMI, whereas the association with SNP-44 was independent of all of 
      these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in 
      humans through the reduction of beta-cell function, with an enhanced effect seen 
      in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 
      SNP-44 have also shown reduced beta-cell function.
FAU - Diaz-Villasenor, Andrea
AU  - Diaz-Villasenor A
AD  - Departmento de Medicina Genomica y Toxicologia Ambiental, Instituto de 
      Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, 
      Mexico.
FAU - Cruz, Laura
AU  - Cruz L
FAU - Cebrian, Arturo
AU  - Cebrian A
FAU - Hernandez-Ramirez, Raul U
AU  - Hernandez-Ramirez RU
FAU - Hiriart, Marcia
AU  - Hiriart M
FAU - Garcia-Vargas, Gonzalo
AU  - Garcia-Vargas G
FAU - Bassol, Susana
AU  - Bassol S
FAU - Sordo, Monserrat
AU  - Sordo M
FAU - Gandolfi, A Jay
AU  - Gandolfi AJ
FAU - Klimecki, Walter T
AU  - Klimecki WT
FAU - Lopez-Carillo, Lizbeth
AU  - Lopez-Carillo L
FAU - Cebrian, Mariano E
AU  - Cebrian ME
FAU - Ostrosky-Wegman, Patricia
AU  - Ostrosky-Wegman P
LA  - eng
GR  - P30 ES006694/ES/NIEHS NIH HHS/United States
GR  - P42 ES004940/ES/NIEHS NIH HHS/United States
GR  - ES-04940/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130122
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Environmental Pollutants)
RN  - 0 (Insulin)
RN  - EC 3.4.22.- (Calpain)
RN  - EC 3.4.22.- (calpain 10)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arsenic/*toxicity
MH  - Calpain/*genetics
MH  - Diabetes Mellitus, Type 2/etiology/genetics/*pathology/physiopathology
MH  - Environmental Exposure/*adverse effects
MH  - Environmental Pollutants/toxicity
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Resistance/genetics
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/*cytology/drug effects/metabolism/*pathology
MH  - Male
MH  - Middle Aged
MH  - Pilot Projects
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
PMC - PMC3551951
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/26 06:00
MHDA- 2013/07/10 06:00
PMCR- 2013/01/22
CRDT- 2013/01/26 06:00
PHST- 2012/07/02 00:00 [received]
PHST- 2012/11/02 00:00 [accepted]
PHST- 2013/01/26 06:00 [entrez]
PHST- 2013/01/26 06:00 [pubmed]
PHST- 2013/07/10 06:00 [medline]
PHST- 2013/01/22 00:00 [pmc-release]
AID - PONE-D-12-19066 [pii]
AID - 10.1371/journal.pone.0051642 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e51642. doi: 10.1371/journal.pone.0051642. Epub 2013 Jan 22.