Obesity Research

Open journal

ISSN 2377-8385

Coenzyme Q10, Glucose Homeostasis and the Probable Mediating Role of Adipokines

Mohammad Javad Hosseinzadeh-Attar*, Elham Alipoor and Parvaneh Mehrdadi

Received: April 22nd, 2016; Accepted: April 22nd, 2016; Published: April 25th, 2016

Coenzyme Q10 is one of the most popular nutritional supplements, which has been discovered in 1955. It is also known as ubiquinone, Q10, CoQ and vitamin Q10. This coenzyme has two isoforms; the oxidized form, ubiquinone, is an electron carrier in mitochondrial respiratory chain and the reduced form, ubiquinol, acts as an antioxidant.1,2 Studies reported its beneficial effects in some diseases such as diabetes, heart failure, hypertension, and Parkinson disease.3,4 Q10 has also been proposed to be helpful in prevention and treatment of neurodegenerative and mitochondrial related diseases.5 Q10 could potentially be effective on metabolic disorders including lipid profile, blood pressure, glycemic control and insulin resistance in different diseases.6,7,8

Many diseases are accompanied with imapired glycemic control and insulin resistance.9 Phosphorylation of Insulin Receptor Substrates (IRS) is crucial for insulin signalling cascade, which in turn activates the mitogen-activated protein kinase (MAP-Kinase) with major mitogenic effects and phosphatidylinositol-3-Kinase (PI-3K) with prominent metabolic properties including appropriate cellular glucose distribution.10 Coenzyme Q10 might induce the tyrosine kinase and phosphatidylinositol 3 kinase (PI3k) activity in liver. These enzymes are involved in improving insulin cascade and increasing GLUT2 and tyrosine phosphorylation of IRS-1, which could in turn enhance glucose uptake and inhibit gluconeogenesis in liver.11 This antioxidant has been shown to reduce HbA1C levels in experimental and clinical studies and to improve long term glycemic control.6,7,12,13 It could also increase insulin production and secretion probably by stimulating ATP generation in pancreatic beta cells.14 Other proposed mechanisms include regulation of insulin receptors, glucose transporters, lipid profile, redox system, and receptors of advanced glycated end products.15

Obesity, the major growing health problem worldwide, is one the most important contributors of initiation and progression of insulin resistance.16 The potential mechanisms include higher production of fatty acids, activation of Toll-like receptor 4 and the innate immune system, alterations in endocrine and inflammatory mediators and activation of nuclear factor-κB (NF-κB).17 Recently the metabolic functions of adipose derived peptides, adipokines, have been investigated progressively in different disorders. The changes in the secretion of adipokines in obesity could inhibit insulin signalling through increasing inflammatory adipocytokines and other mediators interfering the IRS phosphorylation and integrity.17

The relationship between the major adipokines, leptin, adiponectin, resistin and visfatin with glucose homeostasis has previously been demonstrated.18,19 Leptin could contribute to glucose homeostasis through direct and indirect actions on peripheral tissues. Direct leptin actions might inhibit insulin and glucagon secretion from pancreatic cells. Moreover, leptin could potentially affect insulin signaling in adipocytes, liver and skeletal muscles. Central leptin actions on glucose homeostasis might be mediated through both the sympathetic nervous system and the parasympathetic nervous system in different tissues.20 Resistin has primarily been known as an adipokine with adverse effects on insulin sensitivity. Resistin could activate NF-κB and induce the secretion of pro-inflammatory factors, which could be potentially involved in insulin resistance.19 Visfatin has similar inflammatory characteristics; however, regardless of some controversies, it is proposed to have favourable effects on glucose metabolism.21 Moreover, the reduction in adiponectin levels would be associated with insulin resistance, dyslipidemia, metabolic syndrome and atherosclerosis.18 Modulating fatty acid oxidation, reducing hepatic gluconeogenesis and hepatic glucose production are among the proposed mechanisms.22 Adiponectin could also activate adenosine monophosphate dependent kinase and peroxisome proliferator-activated receptor-α pathways.18 There are also recently recognized adipokines with insulin sensitizing features like adipolin (CTRP12).23 Adipolin improves insulin actions by suppressing the gluconeogenesis via PI3K-Akt pathway and improving glucose uptake of adipocytes and hepatocytes. It increases phosphorylation of IRS-1 and Akt in adipose tissue and liver while this effect is not observed in muscle cells.23 Adipolin might also have anti-inflammatory effects. Adipolin administration have decreased macrophages accumulation and the gene expression of proinflammatory cytokines in experimental studies.24

There are obvious commonalities between the mechanisms of modulating glucose metabolism by adipokines and Q10. Nevertheless, despite the available data on the functions of adipokines on insulin signalling, there are few studies investigated the probable role of these peptides in mediating the beneficial effects of dietary supplements such as coenzyme Q10 on glucose homeostasis and insulin resistance. In a recent study, the possible underlying mechanisms of coenzyme Q10 supplementation were assessed in diabetic rats. Regardless of previously documented mechanisms, an increase in adiponectin receptors and levels, and a decrease in visfatin levels were observed.15 Recently, we examined the effects of Q10 on serum adipolin levels and glycemic control of diabetic patients. We observed interesting and unexpected results that will be published soon. These kinds of studies could provide new insights into the possible role of adipocytokines in improving insulin signalling by coenzyme Q10 as a potential adjuvant treatment for conventional anti-diabetic therapies. Further studies investigating the unrecognized mechanisms of the interaction between coenzyme Q10 and adipokines in modulating glucose homeostasis are warranted.

ACKNOWLEDGMENT

The authors appreciate Tehran University of Medical Sciences for their full support.

CONFLICTS OF INTEREST

Dr. Hosseinzadeh-Attar has nothing to disclose.

1. Young AJ, Johnson S, Steffens DC, Doraiswamy PM. Coenzyme Q10: a review of its promise as a neuroprotectant. CNS Spectr. 2007; 12(1): 62-68. doi: 10.1017/S1092852900020538

2. Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001; 20(6): 591-598. doi: 10.1080/07315724.2001.10719063

3. Dhanasekaran M, Ren J. The emerging role of coenzyme Q-10 in aging, neurodegeneration, cardiovascular disease, cancer and diabetes mellitus. Curr Neurovasc Res. 2005; 2(5): 447-459. doi: 10.2174/156720205774962656

4. Khatta M, Alexander BS, Krichten CM, et al. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med. 2000; 132(8): 636-640. doi: 10.7326/0003-4819-132-8-200004180-00006

5. Beal MF. Therapeutic effects of coenzyme Q 10 in neurodegenerative diseases. Methods Enzymol. 2004; 382: 473-487. doi: 10.1016/S0076-6879(04)82026-3

6. Kolahdouz MR, Hosseinzadeh-Attar M, Eshraghian M, Nakhjavani M, Khorami E, Esteghamati A. The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients. Minerva Gastroenterol Dietol. 2013; 59(2): 231-236. Web site. http://europepmc.org/abstract/med/23831913. Accessed April 19, 2016

7. Hodgson J, Watts G, Playford D, Burke V, Croft K. Original communication-coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr. 2002; 56(11): 1137-1142. doi: 10.1038/sj.ejcn.1601464

8. Singh R, Niaz M, Rastogi S, Shukla P, Thakur A. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery. J Hum Hypertens. 1999; 13(3): 203-208. doi: 10.1038/sj.jhh.1000778

9. Semple RK. EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons. Eur J Endocrinol. 2016; 174(5): R209-R223. doi: 10.1530/EJE-15-1131

10. Whiteman EL, Cho H, Birnbaum MJ. Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab. 2002; 13(10): 444- 451. doi: 10.1016/S1043-2760(02)00662-8

11. Amin MM, Asaad GF, Salam RMA, El-Abhar HS, Arbid MS. Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of insulin and adiponectine receptors, tyrosine kinase, PI3K, glucose transporters, sRAGE and visfatin in insulin resistant/diabetic rats. PloS one. 2014; 9(2): e89169. doi: 10.1371/journal.pone.0089169

12. Zahedi H, Eghtesadi S, Seifirad S, et al. Effects of CoQ10 supplementation on lipid profiles and glycemic control in patients with type 2 diabetes: a randomized, double blind, placebo-controlled trial. J Diabetes Metab Disord. 2014; 13(1): 1-8. doi: 10.1186/s40200-014-0081-6

13. Sena CM, Nunes E, Gomes A, et al. Supplementation of coenzyme Q 10 and α-tocopherol lowers glycated hemoglobin level and lipid peroxidation in pancreas of diabetic rats. Nutr Res. 2008; 28(2): 113-121. doi: 10.1016/j.nutres.2007.12.005

14. Mezawa M, Takemoto M, Onishi S, et al. The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: an open label pilot study. Biofactors. 2012; 38(6): 416-421. doi: 10.1002/biof.1038

15. Amin MM, Asaad GF, Abdel Salam RM, El-Abhar HS, Arbid MS. Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of insulin and adiponectine receptors, Tyrosine kinase, PI3K, glucose transporters, sRAGE and visfatin in insulin resistant/diabetic rats. PLoS One. 2014; 9(2): e89169. doi: 10.1371/journal.pone.0089169

16. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006; 444(7121): 840-846. doi: 10.1038/nature05482

17. Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007; 21(12): 1443-1455. doi: 10.1101/gad.1550907

18. Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013; 417: 80-84. doi: 10.1016/j.cca.2012.12.007

19. Stofkova A. Resistin and visfatin: regulators of insulin sensitivity, inflammation and immunity. Endocr Regul. 2010; 44(1): 25- 36. Web site. http://europepmc.org/abstract/med/20151765. Accessed April 19, 2016

20. Denroche HC, Huynh FK, Kieffer TJ. The role of leptin in glucose homeostasis. J Diabetes Investig. 2012; 3(2): 115-129. doi: 10.1111/j.2040-1124.2012.00203.x

21. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005; 365(9467): 1333-1346. doi: 10.1016/S0140-6736(05)61032-X

22. Nedvidkova J, Smitka K, Kopsky V, Hainer V. Adiponectin, an adipocyte-derived protein. Physiol Res. 2005; 54(2): 133-140. Web site. http://search.proquest.com/openview/2443a3956e202092b6c8241770459c20/1?pq-origsite=gscholar. Accessed April 19, 2016

23. Wei Z, Peterson JM, Lei X, et al. C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes. J Biol Chem. 2012; 287(13): 10301-10315. doi: 10.1074/jbc.M111.303651

24. Enomoto T, Ohashi K, Shibata R, et al. Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism. J Biol Chem. 2011; 286(40): 34552-34558. doi: 10.1074/jbc.M111.277319

LATEST ARTICLES

Prevalence and Risk Factors of Subclinical Mastitis of Goats in Banadir Region, Somalia

Omar M. Salah*, Yasin H. Sh-Hassan, Moktar O. S. Mohamed, Mohamed A. Yusuf and Abas S. A. Jimale

doi.10.17140/VMOJ-9-184

Use of Black Soldier Fly (Hermetia illucens) Prepupae Reared on Organic Waste

Maggot Debridement Therapy: A Natural Solution for Wound Healing

Isayas A. Kebede*, Haben F. Gebremeskel and Gelan D. Dahesa,

doi.10.17140/VMOJ-9-183

Figure 11. Risk Map for the Introduction of Ruminant Diseases at Borders

Ovine Network in Morocco: Epizootics Spread Prevention and Identification of the At-Risk Areas for “Peste des Petits Ruminants” and “Foot and Mouth Disease”

Yassir Lezaar*, Mehdi Boumalik, Youssef Lhor, Moha El-Ayachi, Abelilah Araba and Mohammed Bouslikhane

doi.10.17140/EPOJ-8-131

The Impact of Family Dynamics on Palliative Care at the End-of-Life

Neil A. Nijhawan*, Rasha Mustafa and Aqeela Sheikh

doi.10.17140/PMHCOJ-10-154

Long-Term Follow-Up After Laparoscopic Radical Prostatectomy for Localized and Locally Advanced Prostate Cancer

Shrenik J. Shah*, Abhishek Jha, Chirag Davara, Rushi Mistry and Kapil Kachhadiya

doi.10.17140/UAOJ-7-147

Mindfulness, Sustained Attention and Post-Traumatic Stress in Tsunami Survivors

Christina Hagen*, Lars Lien, Edvard Hauff and Trond Heir

doi.10.17140/PCSOJ-2-115

Treatment and Control Methods of Bovine Mastitis: A Review

Isayas A. Kebede* and Gelan D. Dahesa

doi.10.17140/VMOJ-9-182

LATEST ARTICLES

Original Research

2024 Mar

Omar M. Salah*, Yasin H. Sh-Hassan, Moktar O. S. Mohamed, Mohamed A. Yusuf and Abas S. A. Jimale
Use of Black Soldier Fly (Hermetia illucens) Prepupae Reared on Organic Waste

review

2024 Mar

Isayas A. Kebede*, Haben F. Gebremeskel and Gelan D. Dahesa,