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Increased Plasma Manganese, Partially Reduced Ascorbate,1 and Absence of Mitochondrial Oxidative Stress in Type 2 Diabetes Mellitus: Implications for the Superoxide Uncoupling Protein 2 (Ucp-2) Pathway

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Abstract

Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12 females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI) computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K+ levels were determined; K+ was to assess the K+ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide a viable strategy to improve β-cell dysfunction in type 2 diabetes mellitus.

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Acknowledgments

This study was partly supported by a grant from the Senate Research Grant of the University of Ibadan, Ibadan, Nigeria—SRG 2000/016.

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Authors and Affiliations

  1. Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria

    J. I. Anetor, O. A. Asiribo, K. S. Adedapo, O. S. Olorunnisola & F. A. A. Adeniyi

  2. Department of Haematology, College of Medicine, University of Ibadan, Ibadan, Nigeria

    T. S. Akingbola

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  1. J. I. Anetor
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  2. O. A. Asiribo
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  3. K. S. Adedapo
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  4. T. S. Akingbola
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Anetor, J.I., Asiribo, O.A., Adedapo, K.S. et al. Increased Plasma Manganese, Partially Reduced Ascorbate,1 and Absence of Mitochondrial Oxidative Stress in Type 2 Diabetes Mellitus: Implications for the Superoxide Uncoupling Protein 2 (Ucp-2) Pathway. Biol Trace Elem Res 120, 19–27 (2007). https://doi.org/10.1007/s12011-007-0069-x

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  • DOI: https://doi.org/10.1007/s12011-007-0069-x

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