PMID- 29326655
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220314
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 8
DP  - 2017
TI  - Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with 
      Prediabetes and Type 2 Diabetes Mellitus.
PG  - 347
LID - 10.3389/fendo.2017.00347 [doi]
LID - 347
AB  - BACKGROUND AND AIM: Hyperglycemia-mediated oxidative stress impedes 
      cell-reparative process like autophagy, which has been implicated in impairment 
      of beta-cell function in type 2 diabetes mellitus (T2DM). However, the role of 
      mitophagy (selective mitochondrial autophagy) in progression of hyperglycemia 
      remains elusive. This study aimed to assess the impact of increasing severity of 
      hyperglycemia on mitochondrial stress and mitophagy. DESIGN AND METHODS: A 
      case-control study included healthy controls, subjects with prediabetes, newly 
      diagnosed T2DM (NDT2DM) and advanced duration of T2DM (ADT2DM) (n = 20 each). 
      Mitochondrial stress indices, transcriptional and translational expression of 
      mitophagy markers (PINK1, PARKIN, MFN2, NIX, LC3-II, and LAMP-2) and transmission 
      electron microscopic (TEM) studies were performed in peripheral blood mononuclear 
      cells. RESULTS: With mild hyperglycemia in subjects with prediabetes, to moderate 
      to severe hyperglycemia in NDT2DM and ADT2DM, a progressive rise in mitochondrial 
      oxidative stress was observed. Prediabetic subjects exhibited significantly 
      increased expression of mitophagy-related markers and showed a positive 
      association with HOMA-beta, whereas, patients with NDT2DM and ADT2DM demonstrated 
      decreased expression, with a greater decline in ADT2DM subjects. TEM studies 
      revealed significantly reduced number of distorted mitochondria in prediabetics, 
      as compared to the T2DM patients. In addition, receiver operating characteristic 
      analysis showed HbA(1C) > 7% (53 mmol/mol) was associated with attenuated 
      mitophagy. CONCLUSION: Increasing hyperglycemia is associated with progressive 
      rise in oxidative stress and altered mitochondrial morphology. Sustenance of 
      mitophagy at HbA(1C) < 7% (53 mmol/mol) strengthens the rationale of achieving 
      HbA(1C) below this cutoff for good glycemic control. An "adaptive" increase in 
      mitophagy may delay progression to T2DM by preserving the beta-cell function in 
      subjects with prediabetes.
FAU - Bhansali, Shipra
AU  - Bhansali S
AD  - Department of Experimental Medicine and Biotechnology, Postgraduate Institute of 
      Medical Education and Research (PGIMER), Chandigarh, India.
FAU - Bhansali, Anil
AU  - Bhansali A
AD  - Department of Endocrinology, Postgraduate Institute of Medical Education and 
      Research (PGIMER), Chandigarh, India.
FAU - Walia, Rama
AU  - Walia R
AD  - Department of Endocrinology, Postgraduate Institute of Medical Education and 
      Research (PGIMER), Chandigarh, India.
FAU - Saikia, Uma Nahar
AU  - Saikia UN
AD  - Department of Histopathology, Postgraduate Institute of Medical Education and 
      Research (PGIMER), Chandigarh, India.
FAU - Dhawan, Veena
AU  - Dhawan V
AD  - Department of Experimental Medicine and Biotechnology, Postgraduate Institute of 
      Medical Education and Research (PGIMER), Chandigarh, India.
LA  - eng
PT  - Journal Article
DEP - 20171215
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
PMC - PMC5737033
OTO - NOTNLM
OT  - mitochondrial oxidative stress
OT  - mitophagy
OT  - prediabetes
OT  - reactive oxygen species
OT  - type 2 diabetes mellitus
EDAT- 2018/01/13 06:00
MHDA- 2018/01/13 06:01
PMCR- 2017/01/01
CRDT- 2018/01/13 06:00
PHST- 2017/08/22 00:00 [received]
PHST- 2017/11/28 00:00 [accepted]
PHST- 2018/01/13 06:00 [entrez]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/01/13 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2017.00347 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2017 Dec 15;8:347. doi: 10.3389/fendo.2017.00347. 
      eCollection 2017.