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 patho genesis of diabetes mellitus. We recently reported that decreased mtDNA con tent precedes the development of diabetes mellitus and is associated with p arameters of insulin resistance. In this study, we examined whether there i s any relation between mtDNA content and insulin secretion. We compared the mtDNA content of peripheral blood leukocytes with the parameters of insuli n secretion measured by hyperglycemic clamp in a group of healthy young men . There were statistically significant correlations between mtDNA content i n peripheral blood and fasting plasma insulin (r = -0.43. P < 0.05) and C-p eptide levels (r = - 0.44, P < 0.05). MtDNA content also correlated negativ ely with acute insulin response(r = - 0.48, P < 0.05), late insulin respons e (r = - 0.50, P < 0.05) during hyperglycemic clamp and insulin secretion a fter glucagon stimulation (r = - 0.60, P < 0.01). mtDNA content in peripher al blood correlated negatively with homeostasis model (HOMA) insulin resist ance (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 corrolated negatively with indices of insulin resistance and insulin secretion in healthy young men. The compensatory res ponse of pancreas beta cells to insulin resistance might contribute in part to increased insulin secretion in these subjects. (C) 2001 Elsevier Scienc e Ireland Ltd. Ali rights reserved.