Peripheral blood mitochondrial DNA content is inversely correlated with insulin secretion during hyperglycemic clamp studies in healthy young men.

Abnormalities in mitochondrial DNA(mtDNA) have been implicated in the pathogenesis of diabetes mellitus. We recently reported that decreased mtDNA content precedes the development of diabetes mellitus and is associated with parameters of insulin resistance. In this study, we examined whether there is any relation between mtDNA content and insulin secretion. We compared the mtDNA content of peripheral blood leukocytes with the parameters of insulin secretion measured by hyperglycemic clamp in a group of healthy young men. There were statistically significant correlations between mtDNA content in peripheral blood and fasting plasma insulin (r=-0.43, P<0.05) and C-peptide levels (r=-0.44, P<0.05). MtDNA content also correlated negatively with acute insulin response(r=-0.48, P<0.05), late insulin response (r=-0.50, P<0.05) during hyperglycemic clamp and insulin secretion after glucagon stimulation (r=-0.60, P<0.01). mtDNA content in peripheral blood correlated negatively with homeostasis model (HOMA) insulin resistance (r=-0.45, P<0.05) although it did not correlate with the insulin insensitivity index (M/I) during hyperglycemic clamp. In summary, the mtDNA content of peripheral blood correlated negatively with indices of insulin resistance and insulin secretion in healthy young men. The compensatory response of pancreas beta cells to insulin resistance might contribute in part to increased insulin secretion in these subjects.