Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients

Eur J Appl Physiol. 2019 Mar;119(3):813-823. doi: 10.1007/s00421-019-04072-2. Epub 2019 Jan 30.

Abstract

Purpose: Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level.

Methods: Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O2 and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed.

Results: At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT.

Conclusion: IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.

Keywords: Adaptation; Diabetes; Gene Expression; Hypoxia; Insulin; Pyruvate dehydrogenase kinase.

MeSH terms

  • Adaptation, Physiological / physiology
  • Adult
  • Aged
  • Female
  • Humans
  • Hypoxia / physiopathology*
  • Insulin / blood*
  • Leukocytes / cytology*
  • Male
  • Middle Aged
  • Prediabetic State / physiopathology*
  • Protein Serine-Threonine Kinases / blood*
  • Protein Serine-Threonine Kinases / genetics
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RNA, Messenger / genetics

Substances

  • Insulin
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RNA, Messenger
  • Protein Serine-Threonine Kinases