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Peripheral blood mitochondrial DNA content is inversely correlated with insulin secretion during hyperglycemic clamp
1Department of Internal Medicine, Seoul National University College of Medicine, 28 YunKun-Dong, Chongno-Ku, Seoul, 110-744, South Korea.
Abstract:
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.
Insights
Mitochondrial DNA (mtDNA) content in blood cells negatively correlates with insulin resistance and secretion in healthy men. Lower mtDNA may indicate impaired pancreatic beta-cell function, potentially preceding diabetes development.
Area of Science:
- Endocrinology
- Metabolic Research
- Molecular Biology
Background:
- Mitochondrial DNA (mtDNA) abnormalities are linked to diabetes mellitus pathogenesis.
- Previous research indicated decreased mtDNA content precedes diabetes and correlates with insulin resistance.
Purpose of the Study:
- To investigate the relationship between mitochondrial DNA (mtDNA) content and insulin secretion.
- To explore correlations between peripheral blood leukocyte mtDNA levels and insulin secretion parameters.
Main Methods:
- Compared mtDNA content in peripheral blood leukocytes with insulin secretion parameters.
- Utilized hyperglycemic clamp and glucagon stimulation tests in healthy young men.
- Assessed correlations with fasting plasma insulin, C-peptide, HOMA insulin resistance, and acute/late insulin responses.
Main Results:
- Negative correlations were found between mtDNA content and fasting plasma insulin (r=-0.43) and C-peptide levels (r=-0.44).
- Significant negative correlations observed with acute (r=-0.48) and late insulin responses (r=-0.50) during hyperglycemic clamp.
- mtDNA content also correlated negatively with insulin secretion after glucagon stimulation (r=-0.60) and HOMA insulin resistance (r=-0.45).
Conclusions:
- Peripheral blood leukocyte mtDNA content is negatively associated with insulin resistance and insulin secretion in healthy young men.
- The findings suggest that compensatory pancreatic beta-cell responses to insulin resistance may influence insulin secretion.
- Reduced mtDNA content could serve as a potential biomarker for metabolic dysfunction and risk of diabetes.