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Published on: January 23, 2018
Potential relationship between peripheral blood mitochondrial DNA content and insulin resistance and secretion in
Jehan A M el-Sharnooby1, Laila M Sayed Ahmed
1Department of Clinical Pathology, Tanta University, Faculty of Medicine, Tanta, Egypt.
Insights
Mitochondrial DNA (mtDNA) in peripheral blood is lower in offspring of diabetic patients and correlates with insulin resistance and secretion. This suggests mtDNA may be a hereditary factor for type 2 diabetes.
Area of Science:
- Genetics
- Metabolic Diseases
- Molecular Biology
Background:
- Mitochondrial DNA (mtDNA) alterations are linked to diabetes mellitus pathogenesis.
- Investigating peripheral blood mtDNA (pb-mtDNA) in offspring of diabetic individuals is crucial for understanding hereditary risk.
Purpose of the Study:
- To determine if pb-mtDNA content is reduced in offspring of type 2 diabetic patients.
- To explore the relationship between pb-mtDNA levels and markers of insulin resistance and secretion.
Main Methods:
- Quantitative measurement of pb-mtDNA using real-time PCR with a mitochondrial-specific probe.
- Normalization of mtDNA content by a nuclear DNA gene (28S rRNA).
- Correlation analysis between pb-mtDNA and insulin sensitivity/secretion parameters.
Main Results:
- pb-mtDNA levels were significantly lower in offspring of diabetic subjects compared to controls.
- pb-mtDNA content showed significant correlations with insulin sensitivity index, fasting C-peptide, acute insulin response, and late insulin response.
- Negative correlations were observed between pb-mtDNA and indices of insulin resistance and secretion.
Conclusions:
- Quantitative mtDNA status may represent a hereditary factor associated with type 2 diabetes.
- pb-mtDNA content is negatively correlated with insulin resistance and secretion parameters in offspring of diabetic patients.
- pb-mtDNA may serve as a potential indicator of insulin sensitivity and secretion in this population.
Abstract:
Both qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been implicated in the pathogenesis of diabetes mellitus. In this study, we investigate whether peripheral blood mtDNA (pb-mtDNA) is decreased and if there is any relation between its content and the parameters of both insulin resistance and secretion in offspring of diabetic subjects. The pb-mtDNA content was measured by real time polymerase chain reaction with mitochondrial- specific fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene, in 42 offspring of type 2 diabetic patients and 12 age-, sex- and body mass index (BMI)-matched normal subjects. The correlations between pb-mtDNA content and the parameters of insulin resistance and secretion were studied. Our results indicated that the level of pb-mtDNA was lower in offspring of diabetic subjects than in control subjects (1230 +/- 0.05 vs. 1513 +/- 0.02 in the offspring and control subjects, respectively, P < 0.05). Also, pb-mtDNA content was significantly correlated with logarithmically transformed insulin sensitivity index (r = 0.5, P < 0.05), fasting C-peptide (r = -0.8, P < 0.05), acute insulin response (r = -0.8, P < 0.05) and late insulin response (r = -0.7, P < 0.05) in offspring of diabetic subjects. In conclusion, quantitative mtDNA status might be a hereditary factor associated with type 2 diabetes and is correlated negatively with indexes of insulin resistance and insulin secretion in offspring of diabetic patients. So, pb-mtDNA content could serve as an indicator of insulin sensitivity and insulin secretion in those subjects.
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