Accumulation of cadmium in insulin-producing β cells

Malek El Muayed*, Meera R. Raja, Xiaomin Zhang, Keith William Macrenaris, Surabhi Bhatt, Xiaojuan Chen, Margrit Urbanek, Thomas V O'Halloran, William L Lowe Jr

*Corresponding author for this work

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 CdCl2 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.

Original languageEnglish (US)
Pages (from-to)405-416
Number of pages12
JournalIslets
Volume4
Issue number6
DOIs
StatePublished - Nov 1 2012

Fingerprint

Cadmium
Insulin
Oxidative Stress
Cadmium Chloride
Type 2 Diabetes Mellitus
Cultured Cells
Cell Survival
Proteins
Cell Death
Gene Expression
Glucose
Cell Line

Keywords

  • B cells insulin
  • Cadmium
  • Insulin secretion
  • Metallothionein
  • Zinc transporters

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

El Muayed, M., Raja, M. R., Zhang, X., Macrenaris, K. W., Bhatt, S., Chen, X., ... Lowe Jr, W. L. (2012). Accumulation of cadmium in insulin-producing β cells. Islets, 4(6), 405-416. https://doi.org/10.4161/isl.23101
El Muayed, Malek ; Raja, Meera R. ; Zhang, Xiaomin ; Macrenaris, Keith William ; Bhatt, Surabhi ; Chen, Xiaojuan ; Urbanek, Margrit ; O'Halloran, Thomas V ; Lowe Jr, William L. / Accumulation of cadmium in insulin-producing β cells. In: Islets. 2012 ; Vol. 4, No. 6. pp. 405-416.
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Accumulation of cadmium in insulin-producing β cells. / El Muayed, Malek; Raja, Meera R.; Zhang, Xiaomin; Macrenaris, Keith William; Bhatt, Surabhi; Chen, Xiaojuan; Urbanek, Margrit; O'Halloran, Thomas V; Lowe Jr, William L.

In: Islets, Vol. 4, No. 6, 01.11.2012, p. 405-416.

Research output: Contribution to journalArticle

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AU - El Muayed, Malek

AU - Raja, Meera R.

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AB - 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 CdCl2 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.

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El Muayed M, Raja MR, Zhang X, Macrenaris KW, Bhatt S, Chen X et al. Accumulation of cadmium in insulin-producing β cells. Islets. 2012 Nov 1;4(6):405-416. https://doi.org/10.4161/isl.23101