title: Accumulation of cadmium in insulin-producing β cells.
abstract: Evidence suggests that chronic low level cadmium exposure impairs the function of insulin-producing β cells and may be associated with type-2 diabetes mellitus. Herein, we describe the cadmium content in primary human islets and define the uptake kinetics and effects of environmentally relevant cadmium concentrations in cultured β cells. The average cadmium content in islets from 10 non-diabetic human subjects was 29 ± 7 nmol/g protein (range 7 to 72 nmol/g protein). Exposure of the β-cell line MIN6 to CdCl 2 concentrations between 0.1 and 1.0 µmol/L resulted in a dose- and time-dependent uptake of cadmium over 72 h. This uptake resulted in an induction of metallthionein expression, likely enhancing cellular cadmium accumulation. Furthermore, cadmium accumulation resulted in an inhibition of glucose stimulated insulin secretion in MIN6 cells and primary mouse islets. Our results indicate that this impairment in β-cell function is not due to an increase in cell death or due to an increase in oxidative stress. We conclude that mouse β cells accumulate cadmium in a dose- and time-dependent manner over a prolonged time course at environmentally relevant concentrations. This uptake leads to a functional impairment of β-cell function without significant alterations in cell viability, expression of genes important for β-cell function or increase in oxidative stress.
authors: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. m-muayed@northwestern.edu
authors: Malek
authors: M
authors: El Muayed
authors: Meera R
authors: MR
authors: Raja
authors: Xiaomin
authors: X
authors: Zhang
authors: Keith W
authors: KW
authors: MacRenaris
authors: Surabhi
authors: S
authors: Bhatt
authors: Xiaojuan
authors: X
authors: Chen
authors: Margrit
authors: M
authors: Urbanek
authors: Thomas V
authors: TV
authors: O'Halloran
authors: William L
authors: WL
authors: Lowe
mesh_terms: D016475:3T3 Cells; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008628:Mercury / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D027682:Cation Transport Proteins; D007328:Insulin; D012333:RNA, Messenger; D002104:Cadmium; D008628:Mercury
keywords: cadmium; insulin secretion; metallothionein; zinc transporters; β cells