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Toxics. 2018 Mar 22;6(2). pii: E20. doi: 10.3390/toxics6020020.

Mitochondrial Morphology and Function of the Pancreatic β-Cells INS-1 Model upon Chronic Exposure to Sub-Lethal Cadmium Doses.

Author information

1
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. adeline.jacquet1@orange.fr.
2
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. cecile.cottet@univ-grenoble-alpes.fr.
3
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. jarnaud@chu-grenoble.fr.
4
Biochemistry, Molecular Biology and Environmental Toxicology (SB2TE), Grenoble University Hospital, CS 10217, 38043 Grenoble, France. jarnaud@chu-grenoble.fr.
5
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. jsakevin@gmail.com.
6
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. raouabenmessaoud@yahoo.com.
7
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. marine.lenon@hotmail.fr.
8
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. christine.demeilliers@univ-grenoble-alpes.fr.
9
Laboratory of Fundamental and Applied Bioenergetics (LBFA), Inserm, Universite Grenoble Alpes, 38000 Grenoble, France. jean-marc.moulis@cea.fr.
10
CEA-Grenoble, Bioscience and Biotechnology Institute (BIG), 38054 Grenoble, France. jean-marc.moulis@cea.fr.

Abstract

The impact of chronic cadmium exposure and slow accumulation on the occurrence and development of diabetes is controversial for human populations. Islets of Langerhans play a prominent role in the etiology of the disease, including by their ability to secrete insulin. Conversion of glucose increase into insulin secretion involves mitochondria. A rat model of pancreatic β-cells was exposed to largely sub-lethal levels of cadmium cations applied for the longest possible time. Cadmium entered cells at concentrations far below those inducing cell death and accumulated by factors reaching several hundred folds the basal level. The mitochondria reorganized in response to the challenge by favoring fission as measured by increased circularity at cadmium levels already ten-fold below the median lethal dose. However, the energy charge and respiratory flux devoted to adenosine triphosphate synthesis were only affected at the onset of cellular death. The present data indicate that mitochondria participate in the adaptation of β-cells to even a moderate cadmium burden without losing functionality, but their impairment in the long run may contribute to cellular dysfunction, when viability and β-cells mass are affected as observed in diabetes.

KEYWORDS:

bioenergetics; cadmium; image analysis; mitochondrial morphology; mitochondrial network; sub-lethal exposure; toxicological mechanism

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

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