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Mitochondrial Dysfunction in Diabetic Neuropathy: a Series of Unfortunate Metabolic Events

  • Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)
  • Published:
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Abstract

Diabetic neuropathy is a dying back neurodegenerative disease of the peripheral nervous system where mitochondrial dysfunction has been implicated as an etiological factor. Diabetes (type 1 or type 2) invokes an elevation of intracellular glucose concentration simultaneously with impaired growth factor support by insulin, and this dual alteration triggers a maladaptation in metabolism of adult sensory neurons. The energy sensing pathway comprising the AMP-activated protein kinase (AMPK)/sirtuin (SIRT)/peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) signaling axis is the target of these damaging changes in nutrient levels, e.g., induction of nutrient stress, and loss of insulin-dependent growth factor support and instigates an aberrant metabolic phenotype characterized by a suppression of mitochondrial oxidative phosphorylation and shift to anaerobic glycolysis. There is discussion of how this loss of mitochondrial function and transition to overreliance on glycolysis contributes to the diminishment of collateral sprouting and axon regeneration in diabetic neuropathy in the context of the highly energy-consuming nerve growth cone.

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Acknowledgments

This review was funded through Canadian Institutes of Health Research (CIHR) grant number MOP-130282. I thank all my research staff in recent years including Mr. Tarek Habash, Mrs. Kelly Jorundson, Dr. Subir Roy Chowdhury, Dr. Ali Saleh, Ms. Emily Schartner, Darrell Smith DVM, and Mrs. Lori Tessler for their contributions toward the scientific productivity of my laboratory.

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Paul Fernyhough declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, R4046-351 Taché Ave, Winnipeg, Manitoba, R2H 2A6, Canada

    Paul Fernyhough

  2. Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB, R3E 0T6, Canada

    Paul Fernyhough

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Correspondence to Paul Fernyhough.

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http://www.cdc.gov/diabetes/home/index.html—Centers for Disease Control and Prevention, Diabetes home.

This article is part of the Topical Collection on Microvascular Complications—Neuropathy

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Fernyhough, P. Mitochondrial Dysfunction in Diabetic Neuropathy: a Series of Unfortunate Metabolic Events. Curr Diab Rep 15, 89 (2015). https://doi.org/10.1007/s11892-015-0671-9

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