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Current Pharmaceutical Design
ISSN (Print): 1381-6128
ISSN (Online): 1873-4286
VOLUME: 20
ISSUE: 9
DOI: 10.2174/13816128113199990552      Price:  $58









The Heme Oxygenase System and Type-1 Diabetes

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Author(s): Shuchita Tiwari and Joseph Fomusi Ndisang
Pages 1328-1337 (10)
Abstract:
Diabetes is a complex endocrine/metabolic disease with many related complications including micro-vascular and macrovascular problems such as cardiomyopathy, nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by autoimmune- mediated destruction of pancreatic beta cells leading to insulin deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia-mediated oxidative stress, endothelial-cell dysfunction and apoptosis. For decades, type-1 diabetes has been traditionally known as insulin-dependent, while type-2 as non-insulin dependent diabetes. However, it is becoming increasingly clear that insulin deficiency and insulin resistance are manifested in both forms of diabetes at different stages. Thus, it may be time revisit the nomenclature and adjust it to reflect these observations of insulin deficiency and insulin resistance in both forms of diabetes to avoid ambiguity when discussing forms of diabetes.

Emerging evidence indicates that the heme-oxygenase (HO) system and related products including carbon monoxide, ferritin and biliverdin are capable of suppressing immune/inflammatory response, and abate oxidative stress and apoptosis. More importantly, upregulating the HO-system increases pancreatic beta-cell insulin release and reduce hyperglycemia in different diabetic models. Similarly, carbon monoxide, a product of the HO-catalyzed degradation of heme also enhances insulin production and improves glucose metabolism. Since excessive immune/inflammatory responses coupled to elevated apoptosis are among the cardinal pathophysiological features of type-1 diabetes, this review highlights the role of the HO-system and related products such as carbon monoxide and bilirubin in the modulation of apoptosis and immune response, and the beneficial effects of the HO-system in the pathogenesis of type-1 diabetes and related cardiometabolic complications.

Keywords:
Heme oxygenase, oxidative stress, inflammation, immune response.
Affiliation:
Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5.