PMID- 32394161
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Linking)
VI  - 44
IP  - 1
DP  - 2021 Jan
TI  - Insufficient glucocorticoid receptor signaling and flattened salivary cortisol 
      profile are associated with metabolic and inflammatory indices in type 2 
      diabetes.
PG  - 37-48
LID - 10.1007/s40618-020-01260-2 [doi]
AB  - PURPOSE: Impaired negative feedback and hyperactivation of the 
      hypothalamic-pituitary-adrenal (HPA) axis characterizes type 2 diabetes mellitus 
      (T2DM). The glucocorticoid receptor (GR) is a key mediator of HPA axis negative 
      feedback; however, its role in linking hypercortisolemia and T2DM-associated 
      hyperglycemia, hyperlipidemia and inflammation is not yet known. METHODS: In 
      peripheral mononuclear cells (PBMC) from 31 T2DM patients and 24 healthy 
      controls, we measured various GR-signaling parameters such as phosphorylated GR 
      (pGR-S211), GRalpha/GRbeta gene expression and GC-sensitivity [using the basal and 
      dexamethasone (DEX)-induced leucine zipper (GILZ) and FK506 binding-protein 
      (FKBP5) mRNA levels as well as the basal interleukin (IL)-1beta protein levels]. 
      Diurnal salivary cortisol curve parameters such as the cortisol awaking response 
      (CAR) and area under the curve (AUC(total) and AUCi) as well as inflammatory and 
      metabolic indices were also determined. RESULTS: T2DM patients exhibited 
      diminished pGR-S211 protein content, increased GRbeta, decreased basal GILZ and 
      FKBP5 mRNA levels and increased IL-1beta levels. Flattened DEX-induced GILZ and 
      FKBP5 response curves and a flattened salivary cortisol profile characterized 
      T2DM patients. Significant associations of GR measures and saliva cortisol curve 
      parameters with biochemical and clinical characteristics were found. CONCLUSION: 
      Our novel data implicate an insufficient GR signaling in PBMCs in T2DM patients 
      and HPA axis dysfunction. The significant associations of GR-signaling parameters 
      with inflammatory and metabolic indices implicate that GR may be the critical 
      link between HPA axis dysfunction, hypercortisolemia and diabetes-associated 
      metabolic disturbances. Our findings provide significant insights into the 
      contribution of GR-mediated mechanisms in T2DM aetiopathology and therapy.
FAU - Panagiotou, C
AU  - Panagiotou C
AD  - Department of Clinical Biochemistry, National and Kapodistrian University of 
      Athens, School of Medicine, University General Hospital Attikon, Rimini 1, 
      Haidari, 12462, Athens, Greece.
FAU - Lambadiari, V
AU  - Lambadiari V
AD  - Second Department of Internal Medicine and Research Institute, University General 
      Hospital Attikon, Haidari, Greece.
FAU - Maratou, E
AU  - Maratou E
AD  - Department of Clinical Biochemistry, National and Kapodistrian University of 
      Athens, School of Medicine, University General Hospital Attikon, Rimini 1, 
      Haidari, 12462, Athens, Greece.
FAU - Geromeriati, C
AU  - Geromeriati C
AD  - Department of Clinical Biochemistry, National and Kapodistrian University of 
      Athens, School of Medicine, University General Hospital Attikon, Rimini 1, 
      Haidari, 12462, Athens, Greece.
FAU - Artemiadis, A
AU  - Artemiadis A
AD  - Medical School, University of Cyprus, Nicosia, Cyprus.
FAU - Dimitriadis, G
AU  - Dimitriadis G
AD  - Second Department of Internal Medicine and Research Institute, University General 
      Hospital Attikon, Haidari, Greece.
FAU - Moutsatsou, P
AU  - Moutsatsou P
AD  - Department of Clinical Biochemistry, National and Kapodistrian University of 
      Athens, School of Medicine, University General Hospital Attikon, Rimini 1, 
      Haidari, 12462, Athens, Greece. pmoutsatsou@med.uoa.gr.
LA  - eng
GR  - 11SYN_2_741/Greek Secretariat of Research and Technology, Ministry of 
      Development/
PT  - Journal Article
DEP - 20200511
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Receptors, Glucocorticoid)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Biomarkers/*metabolism
MH  - Blood Glucose/analysis
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hydrocortisone/*blood
MH  - Inflammation/etiology/metabolism/*pathology
MH  - Male
MH  - Metabolic Diseases/etiology/metabolism/*pathology
MH  - Middle Aged
MH  - Prognosis
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Saliva/*metabolism
OTO - NOTNLM
OT  - Glucocorticoid receptor
OT  - Glucocorticoid sensitivity
OT  - Inflammation
OT  - Saliva cortisol
OT  - Type 2 diabetes mellitus
EDAT- 2020/05/13 06:00
MHDA- 2021/10/05 06:00
CRDT- 2020/05/13 06:00
PHST- 2020/02/01 00:00 [received]
PHST- 2020/04/15 00:00 [accepted]
PHST- 2020/05/13 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2020/05/13 06:00 [entrez]
AID - 10.1007/s40618-020-01260-2 [pii]
AID - 10.1007/s40618-020-01260-2 [doi]
PST - ppublish
SO  - J Endocrinol Invest. 2021 Jan;44(1):37-48. doi: 10.1007/s40618-020-01260-2. Epub 
      2020 May 11.