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Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)


ISSN (Print): 1871-5222
ISSN (Online): 1875-6115

Lipotoxicity and Mitochondrial Dysfunction in Type 2 Diabetes

Author(s): Matthijs K. C. Hesselink, Marco Mensink and Patrick Schrauwen

Volume 7, Issue 1, 2007

Page: [3 - 17] Pages: 15

DOI: 10.2174/187152207779802509


The prevalence of pre-diabetes and type 2 diabetes increases alarmingly the last few decades and estimates indicate this rise will continue the forthcoming decades. Transition of the pre-diabetic to the diabetic state is a slow but inevitable process. It is therefore of importance to intervene in this transition period in order to prevent overt type 2 diabetes to occur. While the focus of research towards type 2 diabetes has long been glucocentric, over the last decade the focus has shifted to a more lipocentric view. Thus, subnormal fat oxidative capacity, increased mitochondrial damage (lipotoxicity) and decrease mitochondrial function and biogenesis have been identified as factors associated with type 2 diabetes. Within a mitocentric framework, we aim to evaluate the available literature on lipotoxicity and mitochondrial dysfunction and its contribution to the development of insulin resistance and finally type 2 diabetes. In addition, putative targets of intervention will be identified and the modes of action of currently available anti-diabetic agents will be reviewed. In the majority of this review the organ of interest will be the skeletal muscle, as this is the major site of insulin resistance.

Keywords: Fatty acid metabolism, mitochondrial biogenesis, ROS, UCP3

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