alexa Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process
ISSN: 2155-6156

Journal of Diabetes & Metabolism
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Review Article

Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process

Jorge Berlanga-Acosta1*, Pedro López-Saura2, Isabel Guillen-Pérez3, Gerardo Guillen-Nieto1, Boris Acevedo-Castro4, Luis Herrera-Martínez4

1Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Cuba

2Clinical Trials Division, Center for Genetic Engineering and Biotechnology, Cuba

3Pharmacogenomics Department, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Cuba

4Center for Genetic Engineering and Biotechnology, Cuba

*Corresponding Author:
Jorge Berlanga-Acosta
Wound Healing and Cyto-Protection Research Group
Biomedical Research Direction
Center for Genetic Engineering and Biotechnology
Havana 10600, PO Box: 6162, Havana, Cuba
Tel: 53-7-271 60 22
Fax: 53-7-250 44 94
E-mail: [email protected]

Received date: July 16, 2013; Accepted date: August 14, 2013; Published date: August 20, 2013

Citation: Berlanga-Acosta J, López-Saura P, Guillen-Pérez I, Guillen-Nieto G, Acevedo-Castro B, et al. (2013) Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process. J Diabetes Metab 4:285. doi: 10.4172/2155-6156.1000285

Copyright: © 2013 Berlanga-Acosta J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

T2DM is a heterogeneous group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Hyperglycemia may simply represent the tip of a broad series of molecular events from mitochondrial damages, to epigenetic and metabolic pathways deregulations. At the same time, hyperglycemia appears as the most proximal trigger for the onset and perpetual progression of multi-organ complications even under normoglycemic conditions. Thus, the initial hyperglycemic hit translates into a permanently harmful cellular imprinting as has been demonstrated in diabetic donors’ cells after several passages and cultured in ideal conditions. The wound healing failure along with the inability of the innate immunity to control peripheral infections is the hybrid that determines that 85% of all non-traumatic lower extremity amputations are practiced in diabetic subjects. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, cytotoxic reactive oxygen and nitrogen species and a polymicrobial biofilm that impose a stagnant phenotype. All these ingredients negatively impact on fibroblasts, endothelial cells and keratinocytes while paradoxically perpetuate the immuno-inflammatory infiltrate. Although the molecular fundamentals toward chronification have not been elucidated, it seems that different gene simultaneously converge to impose the wound cells a pro-senescent, pro-catabolic and pro-apoptotic phenotype given the lack of a “physiological tuning” of tyrosine kinase-dependent receptors due to their limited activation by insulin and local growth factors. Although recombinant growth factors and smart devices have been introduced during the last years the figures of amputations are still discouraging. Faults have been committed while selecting the appropriate growth factor and because of the “chronic” instinct to treat the chronic wounds topically, where bioavailability of the active principle is compromised by wound and bacterial biofilm proteases. The periodic intralesional infiltration of epidermal growth factor has proved to overcome this hurdle. Granulation tissue growth stimulation and wound healing capacity has been restored in diabetic patients by this procedure in several clinical trials and common clinical practice studies.

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