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Issue 44, 2011
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Metal-based anti-diabetic drugs: advances and challenges

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Abstract

The current status and likely future directions of complexes of V(V/IV), Cr(III), Mo(VI), W(VI), Zn(II), Cu(II), and Mn(III) as potential oral drugs against type 2 diabetes are reviewed. We propose a unified model of extra- and intracellular mechanisms of anti-diabetic efficacies of V(V/IV), Mo(VI), W(VI), and Cr(III), centred on high-oxidation-state oxido/peroxido species that inhibit proteintyrosine phosphatases (PTPs) involved in insulin signalling. The postulated oxidative mechanism of anti-diabetic activity of Cr(III)via carcinogenic Cr(VI/V) (which adds to safety concerns) is consistent with recent clinical trials on Cr(III) picolinate, where activity was apparent only in patients with poorly controlled diabetes (high oxidative stress), and the correlation between the anti-diabetic activities and ease of oxidation of Cr(III) supplements and their metabolitesin vivo.Zn(II) and Cu(II) anti-diabetics act via different mechanisms and are unlikely to be used as specific anti-diabetics due to their diverse and unpredictable biological activities. Hence, future research directions are likely to centre on enhancing the bioavailability and selectivity of V(V/IV), Mo(VI), or W(VI) drugs. The strategy of potentiating circulating insulin with metal ions has distinct therapeutic advantages over interventions that stimulate the release of more insulin, or use insulin mimetics, because of many adverse side-effects of increased levels of insulin, including increased risks of cancer and cardiovascular diseases.

Graphical abstract: Metal-based anti-diabetic drugs: advances and challenges

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Supplementary files

Article information


Submitted
04 Mar 2011
Accepted
23 May 2011
First published
13 Jul 2011

Dalton Trans., 2011,40, 11675-11686
Article type
Perspective

Metal-based anti-diabetic drugs: advances and challenges

A. Levina and P. A. Lay, Dalton Trans., 2011, 40, 11675
DOI: 10.1039/C1DT10380F

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