Increased mitochondrial common deletion in platelets from patients with type 2 diabetes is not associated with abnormal platelet activity or mitochondrial function

Mol Med Rep. 2018 Sep;18(3):3529-3536. doi: 10.3892/mmr.2018.9340. Epub 2018 Jul 31.

Abstract

The present study examined the presence and frequency of the 4,977‑base pair mitochondrial (mt)DNA (mtDNA4977) deletion in blood platelets, and whether increased mtDNA4977 deletion was associated with abnormal mitochondrial and platelet function in type 2 diabetes mellitus. A total of 66 patients with type 2 diabetes mellitus and 23 healthy subjects were included in the present study. Patients were divided into three subgroups according to glycemic control, and the presence or absence of chronic diabetic complications: i) Good glycemic control [glycated hemoglobin (HbA1c) <7] without complications; ii) poor glycemic control (HbA1c ≥7) without complications; and iii) poor glycemic control (HbA1c ≥7) with complications. mtDNA4977 deletion, mtDNA copy number, adenine nucleotides, mitochondrial membrane potential and P‑selectin expression levels were analyzed in platelets. Although the frequency of mtDNA4977 deletion in platelets of the patient (96.9%) and control groups (95.6%) was extremely similar, the deletion level significantly increased in all the diabetic groups, compared with the healthy control group. However, the data from the present study revealed that an increased deletion frequency in platelets was not associated with disease severity, although there was clear interindividual variability. Furthermore, all other parameters were not significantly different among the groups, and there were no correlations between mtDNA4977 deletion frequency and all other studied parameters for any of the case groups. The results indicated that the mtDNA4977 deletion occurred in platelets, and increased deletion in patients with type 2 diabetes did not have a marked influence on mitochondrial and/or platelet dysfunction, when compared with the non‑diabetic subjects. Further research is required to elucidate the sources of inter‑individual variability observed in certain parameters.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism
  • Aged
  • Blood Platelets / metabolism*
  • DNA, Mitochondrial
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Gene Dosage
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • P-Selectin / genetics
  • P-Selectin / metabolism
  • Platelet Activation*
  • Sequence Deletion*

Substances

  • DNA, Mitochondrial
  • P-Selectin
  • Adenosine Diphosphate
  • Adenosine Triphosphate