Glucocorticoid Receptor Signaling in Diabetes
Abstract
1. Introduction
1.1. Stress, Depression and Type 2 Diabetes
1.2. Hypothalamic-Pituitary-Adrenal Axis Hyperactivation and Hypercortisolism in Type 2 Diabetes Mellitus
2. Glucocorticoid Receptor
2.1. Mechanism of Action
2.2. Glucocorticoid Receptor and Metabolism
3. Glucocorticoid Receptor Signaling in Immune Cells in Type 2 Diabetes Mellitus
4. Glucocorticoid Receptor Polymorphisms in Type 2 Diabetes Mellitus
5. The Effects of Micro-RNAs on Glucocorticoid Receptor in Type 2 Diabetes Mellitus
6. Glucocorticoid Receptor and Stevia Glycosides
7. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patients/Sample | GR 1 Signaling Parameters | GC 2 Sensitivity Assay | GC Response | Ref. |
---|---|---|---|---|
T2D 3 patients vs. controls (PBMCs 4) | pGR-S211 protein levels ↓ | [126] | ||
GRβ mRNA levels ↑ | ||||
Basal GILZ mRNA levels ↓ Dex 5-induced GILZ mRNA levels ↓ | Basal and Dex induced expression of GR-stimulated genes | Reduced GC sensitivity (GC resistance) | ||
Basal FKBP5 mRNA levels ↓ Dex-induced FKBP5 mRNA levels ↓ | Basal and Dex induced expression of GR-stimulated genes | Reduced GC sensitivity (GC resistance) | ||
T2D patients vs controls (Whole Blood Cells) | Less capable of producing IL-6 after LPS 6 stimulation Lower Dex concentration needed to inhibit LPS-induced IL-6 | Dex inhibition of LPS-induced IL-6 production | Increased GC sensitivity | [127] |
GR 1 Polymorphisms | GC 2 Response | Refs | Metabolic Indices | Population | Ref. |
---|---|---|---|---|---|
ER22/23EK | GC resistance | [139] | total and LDL 3 cholesterol levels, fasting insulin levels ↓ | Healthy elderly subjects | [139] |
insulin secretion, disposition index ↓ | Women with normal/impaired glucose tolerance | [140] | |||
muscle strength and beneficial body composition ↑ | Healthy subjects | [141] | |||
Tth111I | basal and bedtime salivary cortisol levels ↑ | Middle-aged men | [142] | ||
ER22/23EK and Tth111I | GC resistance | [143] | fasting insulin levels, total and LDL cholesterol levels ↓ | Elderly subjects | [143] |
BclI | Increased GC sensitivity | [148] | body weight, BMI 4 ↑ abdominal obesity fasting plasma glucose, insulin, HOMA 5 ↑ | Swedish men born in 1944 | [144] |
salivary cortisol values after stimulation by a standardized lunch ↑ abdominal obesity | Middle-aged men | [145] | |||
fasting insulin, HOMA↑ | Women with obesity | [146] | |||
total body fatness, insulin resistance ↑ | Participants from CODAM 8 and the Hoorn study | [147] | |||
central adiposity, impaired glucose tolerance, diabetes mellitus, dyslipidemia | Patients with Addison’s disease | [149] | |||
N363S | Increased GC sensitivity | [152] | obesity, weight, BMI, HDL 6 ↑ | Patients with T2D | [153] |
overweight | Patients with T2D | [154] | |||
obesity | Non-diabetic white subjects of British descent | [155] | |||
mRNA levels HSD11B1 ↑ mRNA levels of IGF-1 ↓ mRNA levels of IRS1 ↓ | Healthy subjects | [156] | |||
disposition index ↓ | Women with normal/impaired glucose tolerance | [140] | |||
GR-9β | GC resistance | [159] | risk of obesity ↓ total cholesterol levels ↓ HDL↑ | Europid women | [160] |
risk of developing T2D 7 ↓ | Patients with Cushing’s syndrome | [161] |
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Kokkinopoulou, I.; Diakoumi, A.; Moutsatsou, P. Glucocorticoid Receptor Signaling in Diabetes. Int. J. Mol. Sci. 2021, 22, 11173. https://doi.org/10.3390/ijms222011173
Kokkinopoulou I, Diakoumi A, Moutsatsou P. Glucocorticoid Receptor Signaling in Diabetes. International Journal of Molecular Sciences. 2021; 22(20):11173. https://doi.org/10.3390/ijms222011173
Chicago/Turabian StyleKokkinopoulou, Ioanna, Andriana Diakoumi, and Paraskevi Moutsatsou. 2021. "Glucocorticoid Receptor Signaling in Diabetes" International Journal of Molecular Sciences 22, no. 20: 11173. https://doi.org/10.3390/ijms222011173
APA StyleKokkinopoulou, I., Diakoumi, A., & Moutsatsou, P. (2021). Glucocorticoid Receptor Signaling in Diabetes. International Journal of Molecular Sciences, 22(20), 11173. https://doi.org/10.3390/ijms222011173