An investigation of saliva and plasma levels of urotensin 2 in recently diagnosed type 2 diabetes mellitus patients on metformin treatment
, 1, 2, 1, 3, 4, 5, 6
Abstract
Introduction: Diabetes mellitus (DM) is a primary disease of the carbohydrate metabolism that is characterised by absolute or relative insulin deficiency, or insulin resistance. Although life expectancy is low for diabetic patients, the prognosis has been improved in recent decades. Metformin is an oral antidiabetic that reduces insulin resistance and plasma glucose levels by decreasing glucose production in the liver. It can be used as a standalone treatment or in combination with other antidiabetic medications or insulin. Urotensin 2 (U-II), which is one of the most effective known vasoconstrictor peptides, was observed to act as a vasoconstrictor in diseases such as hypertension and heart failure, and to induce vasodilation in healthy volunteers. Some studies have proposed that the activation of the U-II system could lead to metabolic syndrome. Certain studies have determined a link between DM and U-II. However, there exist no studies on the effects of U-II in recently diagnosed type 2 DM patients after metformin treatment.
This study aims to investigate the plasma and saliva levels of U-II at diagnosis and after a three-month metformin treatment in recently diagnosed type 2 DM patients, and to compare these levels to those of healthy volunteers.
Material and methods: Our study compared 30 recently diagnosed type 2 DM patients to their states after three-month metformin treatment and 30 healthy volunteers.
Results: When compared with the control group, there was no significant increase in the plasma and saliva U-II levels of recently diagnosed type 2 DM patients. We determined a statistically significant increase in the plasma and saliva ureotensin-2 levels of recently diagnosed type 2 DM patients after a three-month metformin treatment (p < 0.05).
Conclusions: It was concluded that the patients with type 2 DM have a multifactorial aetiopathogenesis and an increase in U-II levels after metformin treatment. Metformin has no known effect on the U-II metabolism; therefore, the findings need confirmation through more clinical and experimental studies with more participants.
Keywords: type 2 diabetes mellitusmetforminurotensin 2
References
- Olefsky J. Diabetes mellitus. Cecil Textbook of Medicine. 18th ed. Wynagaarden and Smith Jr, WB Saunders Int 1992: 248–262.
- Güven T. Diabetes Mellitus’lu Hastalarda Yaşam Kalitesi ve Depresyon Etkisinin Araştırılması Uzmanlık Tezi. TC Sağlık Bakanlığı Şişli Etfal Eğitim ve Araştırma Hastanesi Psikiyatri Kliniği, İstanbul 2007.
- Göç DM. Diyabetes Mellitus'lu Hastalarda, Hastalığın Süresi, Hastaların Öğrenim Düzeyi, Diyabetik Ayakla İlgili Eğitim Alma Durumu, Metabolik Değerlerin, Diyabetik Ayak Gelişim Riski ve Diyabetik Ayakdan Koruyucu Davranış Modelleri Geliştirmeye Etkileri. Uzmanlık Tezi. Sağlık Bakanlığı Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, İstanbul 2008.
- Joslin EP, Kahn CR. Joslin's Diabetes Mellitus. Ronald KC (ed). 14th ed.Ronald KC, Kahn CR. ed. Lippincott Williams & Wilkins, 2005 .
- IDF (International Diabetes Federation). IDF Diabetes Atlas, 8th ed. International Diabetes Federation, Belgium: 2017: 161–163.
- Tibaldi J. Importance of postprandial glucose levels as a target for glycemic control in type 2 diabetes. South Med J. 2009; 102(1): 60–66.
- Ong KL, Lam KSL, Cheung BMY. Urotensin II: its function in health and its role in disease. Cardiovasc Drugs Ther. 2005; 19(1): 65–75.
- McDonald J, Batuwangala M, Lambert DG. Role of urotensin II and its receptor in health and disease. J Anesth. 2007; 21(3): 378–389.
- Vaudry H, Leprince J, Chatenet D, et al. International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function. Pharmacol Rev. 2015; 67(1): 214–258.
- Totsune K, Takahashi K, Arihara Z, et al. Increased plasma urotensin II levels in patients with diabetes mellitus. Clin Sci (Lond). 2003; 104(1): 1–5.
- Langham RG, Kelly DJ, Gow RM, et al. Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy. Am J Kidney Dis. 2004; 44(5): 826–831.
- Djordjevic T, BelAiba RS, Bonello S, et al. Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells. Arterioscler Thromb Vasc Biol. 2005; 25(3): 519–525.
- Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999; 48(1): 1–9.
- El-Remessy AB, Behzadian MA, Abou-Mohamed G, et al. Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor. Am J Pathol. 2003; 162(6): 1995–2004.
- Suguro T, Watanabe T, Kodate S, et al. Increased plasma urotensin-II levels are associated with diabetic retinopathy and carotid atherosclerosis in Type 2 diabetes. Clin Sci (Lond). 2008; 115(11): 327–334.
- Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides. 2015; 72: 4–15.
- Ong KL, Lam KSL, Cheung BMY. Urotensin II: its function in health and its role in disease. Cardiovasc Drugs Ther. 2005; 19(1): 65–75.
- McDonald J, Batuwangala M, Lambert DG. Role of urotensin II and its receptor in health and disease. J Anesth. 2007; 21(3): 378–389.
- Bousette N, Patel L, Douglas SA, et al. Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta. Atherosclerosis. 2004; 176(1): 117–123.
- Ong KL, Lam KSL, Cheung BMY. Urotensin II: its function in health and its role in disease. Cardiovasc Drugs Ther. 2005; 19(1): 65–75.
- Nazer RI, Abalhassan MF, Alburikan KA. Liver enzyme trends in patients taking uninterrupted metformin before and after coronary surgery. Cardiovasc Diagn Ther. 2018; 8(4): 469–479.
- Anushiravani A, Haddadi N, Pourfarmanbar M, et al. Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial. Eur J Gastroenterol Hepatol. 2019; 31(5): 613–617.
- Shaker M, Mashhadani ZI, Mehdi AA. Effect of Treatment with Metformin on Omentin-1, Ghrelin and other Biochemical, Clinical Features in PCOS Patients. Oman Med J. 2010; 25(4): 289–293.
- Totsune K, Takahashi K, Arihara Z, et al. Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with Type 2 diabetes mellitus: association with progress of diabetic nephropathy. Peptides. 2004; 25(10): 1809–1814.
- Calan M, Arkan T, Kume T, et al. The relationship between urotensin II and insulin resistance in women with gestational diabetes mellitus. Hormones (Athens). 2019; 18(1): 91–97.
- Hursitoglu M, Ekiz A, Mete F, et al. Plasma Urotensin II concentration in gestational diabetes. Arch Clin Exp Med. 2017; 2: 66–70.
- Tabur S, Korkmaz H, Eren MA, et al. Urotensin-II level and its association with oxidative stress in early diabetic nephropathy. J Diabetes Complications. 2015; 29(1): 115–119.
- Gruson D, Rousseau MF, Ketelslegers JM, et al. Raised plasma urotensin II in type 2 diabetes patients is associated with the metabolic syndrome phenotype. J Clin Hypertens (Greenwich). 2010; 12(8): 653–660.
- Sidharta PN, Rave K, Heinemann L, et al. Effect of the urotensin-II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus. Br J Clin Pharmacol. 2009; 68(4): 502–510.
