beta-Cell function in individuals carrying the mitochondrial tRNA Leu (UUR) mutation
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2007-01-01
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Objectives: To assess the beta-cell function in individuals with mitochondrial DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme Q10 supplementation on insulin secretory response.Methods: Eight mutation-positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell function was evaluated by C-peptide levels before and after a mixed liquid meal (Sustacal) challenge and by first-phase insulin response.Results: Fasting and Sustacal-stimulated C-peptide levels were significantly lower in diabetic patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/- 173.8, P = 0.001), whereas in individuals with NGT, this response was preserved (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). the duration of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961, P = 0.038). Among the 3 patients with residual insulin secretion, the short-term treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them. the first-phase insulin response was diminished in 2 individuals with NGT, the oldest ones.Conclusions: We showed an impaired insulin secretory capacity in individuals carrying the A3243G mutation, this possibly being the primary defect contributing to the development of DM. in addition, our data suggest that this could be a functional defect.
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Pancreas. Philadelphia: Lippincott Williams & Wilkins, v. 34, n. 1, p. 133-137, 2007.