Relationship between insulin resistance and endogenous cannabinoid receptor 1 protein expression of PBMC in OSAHS patients_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 WANG Xiaoya , PU Jiayuan , BAI Xue , LU Wenqiang , FENG Tao

Department of Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P. R. China;

Corresponding author：

WANG Xiaoya, Email: wxy750519@163.com

Keywords：

Obstructive sleep apnea-hypopnea syndrome; Insulin resistance; Endocannabinoid; Diabetes mellitus

DOI：

10.7507/1671-6205.201706024

Video：

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ObjectiveTo investigate the relationship between glucose metabolism and endocannabinoid system (ECS) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).MethodsA total of 64 OSAHS patients (18 cases of mild OSAHS, 24 cases of moderate OSAHS, 22 cases of severe OSAHS) and 24 controls were included in the study. Body mass index, waist circumference, fasting blood lipids, fasting blood glucose, fasting blood insulin, homeostasis model of assessment for insulin resistance index (HOMA-IR), polysomnography and endogenous cannabinoid receptor 1 (CB1R) protein expression levels in peripheral blood mononuclear cells (PBMC) were measured in participants.ResultsThe incidence of diabetes and impaired fasting glucose (IFG) in the OSAHS group was significantly higher than that in the control group (28.12% vs. 8.33%). With the increase of apnea hypopnea index (AHI), HOMA-IR and the expression levels of CB1R protein increased gradually (HOMA-IR: 2.40±0.90, 2.34±0.59, 2.94±0.99, 3.46±0.77, respectively; CB1R protein: 0.04±0.01, 0.37±0.09, 0.40±0.07, 0.62±0.14, respectively). Correlation analysis showed that HOMA-IR, AHI and the expression of CB1R protein were significantly positively correlated with each other (P<0.05).ConclusionOSAHS patients are prone to insulin resistance, IFG and diabetes mellitus, which are closely related to the activation of ECS induced by OSAHS.

Citation： WANG Xiaoya, PU Jiayuan, BAI Xue, LU Wenqiang, FENG Tao. Relationship between insulin resistance and endogenous cannabinoid receptor 1 protein expression of PBMC in OSAHS patients. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(4): 383-389. doi: 10.7507/1671-6205.201706024 Copy

1.	Pamidi S, Tasali E. Obstructive sleep apnea and type 2 diabetes: is there a link?. Front Neurol, 2012, 3: 126.
2.	Carreras A, Kayali F, Zhang J, et al. Metabolic effects of intermittent hypoxia in mice: steady versus high-frequency applied hypoxia daily during the rest period. Am J Physiol Regul Integr Comp Physiol, 2012, 303(7): R700-R709.
3.	Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry, 2016, 79(7): 516-525.
4.	Benyo Z, Ruisanchez E, Leszl-Ishiguro M, et al. Endocannabinoids in cerebrovascular regulation. Am J Physiol Heart Circ Physiol, 2016, 310(7): H785-H801.
5.	Maccarrone M. Metabolism of the endocannabinoid anandamide: open questions after 25 years. Front Mol Neurosci, 2017, 10: 166.
6.	Engeli S, Bluher M, Jumpertz R, et al. Circulating anandamide and blood pressure in patients with obstructive sleep apnea. J Hypertens, 2012, 30(12): 2345-2351.
7.	Jumpertz R, Wiesner T, Bluher M, et al. Circulating endocannabinoids and N-acyl-ethanolamides in patients with sleep apnea--specific role of oleoylethanolamide. Exp Clin Endocrinol Diabetes, 2010, 118(9): 591-595.
8.	Galiegue S, Mary S, Marchand J, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem,1995, 232(1): 54-61.
9.	Jean-Gilles L, Braitch M, Latif ML, et al. Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells. Acta physiologica, 2015, 214(1): 63-74.
10.	Almestrand S, Wang X, Jeppsson-Ahlberg A, et al. Influence of rimonabant treatment on peripheral blood mononuclear cells; flow cytometry analysis and gene expression profiling. Peer J, 2015, 3: e1056.
11.	Goto S, Takahashi R, Radak Z, et al. Beneficial biochemical outcomes of late-onset dietary restriction in rodents. Ann N Y Acad Sci, 2007, 1100: 431-441.
12.	Nong L, Newton C, Friedman H, et al. CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types. Adv Exp Med Biol, 2001, 493: 229-233.
13.	中华医学会呼吸病学分会睡眠呼吸障碍学组. 阻塞性睡眠呼吸暂停低通气综合征诊治指南(2011年修订版). 中华结核和呼吸杂志, 2012, 35(1): 162-165.
14.	Yang J, Park Y, Zhang H, et al. Feed-forward signaling of TNF-alpha and NF-kappaB via IKK-beta pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice. Am J Physiol Heart Circulatory Physiol, 2009, 296(6): H1850-H1858.
15.	Damanti S, Bourron O, Doulazmi M, et al. Relationship between sleep parameters, insulin resistance and age-adjusted insulin like growth factor-1 score in non diabetic older patients. PLoS one, 2017, 12(4): e0174876.
16.	Hargens TA, Guill SG, Kaleth AS, et al. Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea. Sleep Breath, 2013, 17(1): 403-409.
17.	Coughlin SR, Mawdsley L, Mugarza JA, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J, 2007, 29(4): 720-727.
18.	Iiyori N, Alonso LC, Li J, et al. Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med, 2007, 175(8): 851-857.
19.	Yokoe T, Alonso LC, Romano LC, et al. Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic beta-cell replication in mice. J Physiol, 2008, 586(3): 899-911.
20.	Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol, 2012, 13(6): 383-396.
21.	Wasilewski A, Krajewska U, Owczarek K, et al. Fatty acid amide hydrolase (FAAH) inhibitor PF-3845 reduces viability, migration and invasiveness of human colon adenocarcinoma Colo-205 cell line: an in vitro study. Acta Biochimica Polonica, 2017, 64(3): 519-525.
22.	de Luis DA, Izaola O, Aller R, et al. Effects of C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) on weight loss, adipocytokines levels, and insulin resistance after a high polyunsaturated fat diet in obese patients. J Endocrinol Invest, 2013, 36(11): 965-969.
23.	Pallayova M, Lazurova I, Donic V. Hypoxic damage to pancreatic beta cells--the hidden link between sleep apnea and diabetes. Medical hypotheses, 2011, 77(5): 930-934.
24.	Muller T, Demizieux L, Troy-Fioramonti S, et al. Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue. Am J Physiol Endocrinol Metab, 2017, 313(1): E26-E36.
25.	Walter C, Ferreiros N, Bishay P, et al. Exogenous delta(9)-tetrahydrocannabinol influences circulating endogenous cannabinoids in humans. J Clin Psychopharmacol, 2013, 33(5): 699-705.
26.	Gatta-Cherifi B, Cota D. New insights on the role of the endocannabinoid system in the regulation of energy balance. International journal of obesity, 2016, 40(2): 210-219.
27.	张晓英, 王鹏翔, 张致英,等. 红景天苷改善胰岛素抵抗 HepG2 细胞糖代谢及分子机制初探. 中药药理与临床, 2014, 30(1): 28-31.
28.	Richey JM, Woolcott O. Re-visiting the Endocannabinoid system and its therapeutic potential in obesity and associated diseases. Curr Diab Rep, 2017, 17(10): 99.
29.	Yang D, Liu Z, Yang H, et al. Effects of continuous positive airway pressure on glycemic control and insulin resistance in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath, 2013, 17(1): 33-38.
30.	Lipina C, Vaanholt LM, Davidova A, et al. CB1 receptor blockade counters age-induced insulin resistance and metabolic dysfunction. Aging cell, 2016, 15(2): 325-335.
31.	Hecht L, Mohler R, Meyer G. Effects of CPAP-respiration on markers of glucose metabolism in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis. Ger Med Sci 2011, 9: Doc20.
32.	Nam DH, Lee MH, Kim JE, et al. Blockade of cannabinoid receptor 1 improves insulin resistance, lipid metabolism, and diabetic nephropathy in db/db mice. Endocrinology, 2012, 153(3): 1387-1396.
33.	Chen L, Cao ZL, Han F, et al. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.Chin Med J (Engl), 2010, 123(4): 463-470.
34.	Wang N, Khan SA, Prabhakar NR, et al. Impairment of pancreatic beta-cell function by chronic intermittent hypoxia. Exp Physiol, 2013, 98(9): 1376-1385.
35.	Engeli S, Bohnke J, Feldpausch M, et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005, 54(10): 2838-2843.

1. Pamidi S, Tasali E. Obstructive sleep apnea and type 2 diabetes: is there a link?. Front Neurol, 2012, 3: 126.
2. Carreras A, Kayali F, Zhang J, et al. Metabolic effects of intermittent hypoxia in mice: steady versus high-frequency applied hypoxia daily during the rest period. Am J Physiol Regul Integr Comp Physiol, 2012, 303(7): R700-R709.
3. Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry, 2016, 79(7): 516-525.
4. Benyo Z, Ruisanchez E, Leszl-Ishiguro M, et al. Endocannabinoids in cerebrovascular regulation. Am J Physiol Heart Circ Physiol, 2016, 310(7): H785-H801.
5. Maccarrone M. Metabolism of the endocannabinoid anandamide: open questions after 25 years. Front Mol Neurosci, 2017, 10: 166.
6. Engeli S, Bluher M, Jumpertz R, et al. Circulating anandamide and blood pressure in patients with obstructive sleep apnea. J Hypertens, 2012, 30(12): 2345-2351.
7. Jumpertz R, Wiesner T, Bluher M, et al. Circulating endocannabinoids and N-acyl-ethanolamides in patients with sleep apnea--specific role of oleoylethanolamide. Exp Clin Endocrinol Diabetes, 2010, 118(9): 591-595.
8. Galiegue S, Mary S, Marchand J, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem,1995, 232(1): 54-61.
9. Jean-Gilles L, Braitch M, Latif ML, et al. Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells. Acta physiologica, 2015, 214(1): 63-74.
10. Almestrand S, Wang X, Jeppsson-Ahlberg A, et al. Influence of rimonabant treatment on peripheral blood mononuclear cells; flow cytometry analysis and gene expression profiling. Peer J, 2015, 3: e1056.
11. Goto S, Takahashi R, Radak Z, et al. Beneficial biochemical outcomes of late-onset dietary restriction in rodents. Ann N Y Acad Sci, 2007, 1100: 431-441.
12. Nong L, Newton C, Friedman H, et al. CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types. Adv Exp Med Biol, 2001, 493: 229-233.
13. 中华医学会呼吸病学分会睡眠呼吸障碍学组. 阻塞性睡眠呼吸暂停低通气综合征诊治指南(2011年修订版). 中华结核和呼吸杂志, 2012, 35(1): 162-165.
14. Yang J, Park Y, Zhang H, et al. Feed-forward signaling of TNF-alpha and NF-kappaB via IKK-beta pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice. Am J Physiol Heart Circulatory Physiol, 2009, 296(6): H1850-H1858.
15. Damanti S, Bourron O, Doulazmi M, et al. Relationship between sleep parameters, insulin resistance and age-adjusted insulin like growth factor-1 score in non diabetic older patients. PLoS one, 2017, 12(4): e0174876.
16. Hargens TA, Guill SG, Kaleth AS, et al. Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea. Sleep Breath, 2013, 17(1): 403-409.
17. Coughlin SR, Mawdsley L, Mugarza JA, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J, 2007, 29(4): 720-727.
18. Iiyori N, Alonso LC, Li J, et al. Intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. Am J Respir Crit Care Med, 2007, 175(8): 851-857.
19. Yokoe T, Alonso LC, Romano LC, et al. Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic beta-cell replication in mice. J Physiol, 2008, 586(3): 899-911.
20. Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol, 2012, 13(6): 383-396.
21. Wasilewski A, Krajewska U, Owczarek K, et al. Fatty acid amide hydrolase (FAAH) inhibitor PF-3845 reduces viability, migration and invasiveness of human colon adenocarcinoma Colo-205 cell line: an in vitro study. Acta Biochimica Polonica, 2017, 64(3): 519-525.
22. de Luis DA, Izaola O, Aller R, et al. Effects of C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) on weight loss, adipocytokines levels, and insulin resistance after a high polyunsaturated fat diet in obese patients. J Endocrinol Invest, 2013, 36(11): 965-969.
23. Pallayova M, Lazurova I, Donic V. Hypoxic damage to pancreatic beta cells--the hidden link between sleep apnea and diabetes. Medical hypotheses, 2011, 77(5): 930-934.
24. Muller T, Demizieux L, Troy-Fioramonti S, et al. Overactivation of the endocannabinoid system alters the antilipolytic action of insulin in mouse adipose tissue. Am J Physiol Endocrinol Metab, 2017, 313(1): E26-E36.
25. Walter C, Ferreiros N, Bishay P, et al. Exogenous delta(9)-tetrahydrocannabinol influences circulating endogenous cannabinoids in humans. J Clin Psychopharmacol, 2013, 33(5): 699-705.
26. Gatta-Cherifi B, Cota D. New insights on the role of the endocannabinoid system in the regulation of energy balance. International journal of obesity, 2016, 40(2): 210-219.
27. 张晓英, 王鹏翔, 张致英,等. 红景天苷改善胰岛素抵抗 HepG2 细胞糖代谢及分子机制初探. 中药药理与临床, 2014, 30(1): 28-31.
28. Richey JM, Woolcott O. Re-visiting the Endocannabinoid system and its therapeutic potential in obesity and associated diseases. Curr Diab Rep, 2017, 17(10): 99.
29. Yang D, Liu Z, Yang H, et al. Effects of continuous positive airway pressure on glycemic control and insulin resistance in patients with obstructive sleep apnea: a meta-analysis. Sleep Breath, 2013, 17(1): 33-38.
30. Lipina C, Vaanholt LM, Davidova A, et al. CB1 receptor blockade counters age-induced insulin resistance and metabolic dysfunction. Aging cell, 2016, 15(2): 325-335.
31. Hecht L, Mohler R, Meyer G. Effects of CPAP-respiration on markers of glucose metabolism in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis. Ger Med Sci 2011, 9: Doc20.
32. Nam DH, Lee MH, Kim JE, et al. Blockade of cannabinoid receptor 1 improves insulin resistance, lipid metabolism, and diabetic nephropathy in db/db mice. Endocrinology, 2012, 153(3): 1387-1396.
33. Chen L, Cao ZL, Han F, et al. Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.Chin Med J (Engl), 2010, 123(4): 463-470.
34. Wang N, Khan SA, Prabhakar NR, et al. Impairment of pancreatic beta-cell function by chronic intermittent hypoxia. Exp Physiol, 2013, 98(9): 1376-1385.
35. Engeli S, Bohnke J, Feldpausch M, et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005, 54(10): 2838-2843.

Chinese Journal of Respiratory and Critical Care Medicine

Relationship between insulin resistance and endogenous cannabinoid receptor 1 protein expression of PBMC in OSAHS patients

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