Sodium arsenite impairs insulin secretion and transcription in pancreatic beta-cells.
Human studies have shown that chronic inorganic arsenic (iAs) exposure is associated with a high prevalence and incidence of type 2 diabetes. However, the mechanism(s) underlying this effect are not well understood, and practically, there is no information available on the effects of arsenic on pancreatic beta-cells functions. Thus, since insulin secreted by the pancreas plays a crucial role in maintaining glucose homeostasis, our aim was to determine if sodium arsenite impairs insulin secretion and mRNA expression in single adult rat pancreatic beta-cells. Cells were treated with 0.5, 1, 2, 5 and 10 microM sodium arsenite and incubated for 72 and 144 h. The highest dose tested (10 microM) decreased beta-cell viability, by 33% and 83%, respectively. Insulin secretion and mRNA expression were evaluated in the presence of 1 and 5 microM sodium arsenite. Basal insulin secretion, in 5.6 mM glucose, was not significantly affected by 1 or 5 microM treatment for 72 h, but basal secretion was reduced when cells were exposed to 5 microM sodium arsenite for 144 h. On the other hand, insulin secretion in response to 15.6 mM glucose decreased with sodium arsenite in a dose-dependent manner in such a way that cells were no longer able to distinguish between different glucose concentrations. We also showed a significant decrease in insulin mRNA expression of cells exposed to 5 microM sodium arsenite during 72 h. Our data suggest that arsenic may contribute to the development of diabetes mellitus by impairing pancreatic beta-cell functions, particularly insulin synthesis and secretion.
Díaz-Villaseñor
Andrea
A
Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México.
Sánchez-Soto
M Carmen
MC
Cebrián
Mariano E
ME
Ostrosky-Wegman
Patricia
P
Hiriart
Marcia
M
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D018053:Arsenites; D007328:Insulin; D012333:RNA, Messenger; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; C017947:sodium arsenite