Available online at www.sciencedirect.com Digestive and Liver Disease 41 (2009) 253–262 Alimentary Tract Endothelial nitric oxide synthase (eNOS) is not upregulated in gastric mucosa of Helicobacter pylori (H. pylori)-positive patients with type 2 diabetes mellitus G. Lazaraki a,∗ , J. Kountouras b , S. Metallidis a , E. Vrettou c , M. Alevizos d , V. Tzioufa c , S. Dokas d , G. Germanidis a , C. Zavos b , P. Nikolaidis a a First Department of Internal Medicine, Gastroenterology Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54006 Thessaloniki, Greece b Department of Gastroenterology, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece c Pathology University Department, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54006 Thessaloniki, Greece d First Propaedeutic Department of Internal Medicine, Diabetes Mellitus Clinic, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Received 19 April 2008; accepted 16 June 2008 Available online 26 July 2008 Abstract Aim. To evaluate the expression of eNOS and CD34 in gastric mucosa of Helicobacter pylori (H. pylori) positive diabetic patients, in correlation with glycaemic control and diabetic autonomic neuropathy (DAN). Methods. We prospectively studied 49 diabetic type 2 patients (29 women, mean age 65.32 ± 8.56 years) and 30 control subjects (15 women, mean age 58.47 ± 12.40) that underwent endoscopy. Biopsies from the body and antrum were evaluated for H. pylori-gastritis, eNOS and angiogenic marker CD34 expression. Statistical analysis in correlation with mean glycosylated haemoglobin (HbA1c) of the last 3 years, and DAN was performed. Results. The two groups were matched for age (p = 0.144), sex (p = 0.335), H. pylori-infection (p = 0.617) and degree of gastritis (p = 0.78). eNOS and CD34 attenuated expression correlated with diabetes mellitus (DM) in the corpus (p = 0.009 and 0.02, respectively). eNOS and CD34 expression was upregulated in H. pylori-positive controls but not in H. pylori-positive diabetic patients (p = 0.010 and 0.007 for the corpus and p = 0.036 and 0.047 for the antrum, respectively). eNOS expression correlated with good glycaemic control (GGC) in the gastric corpus (p < 0.001) and antrum (p = 0.0037) and with absence of DAN (p = 0.009 and 0.036, respectively for the corpus and antrum). Conclusion. Chronic glycaemic control affects eNOS expression and angiogenesis in the gastric mucosa of patients with type 2 DM. eNOS expression is not upregulated in H. pylori-positive diabetic patients. © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: eNOS; Nitric oxide; Diabetes; Gastric defence; Submucosal blood flow; Angiogenesis; H. pylori 1. Introduction Nitric oxide (NO) plays a multifaceted role in mucosal integrity. The several functions of NO and the double-edged role played by NO in most of them provide a great complexity ∗ Corresponding author at: 14 Papadaki Street, 54248 Thessaloniki, Greece. Tel.: +30 2310 317602; fax: +30 2310 898408. E-mail address: lazarakg@yahoo.com (G. Lazaraki). to the NO action. The three enzymatic sources of NO, neu- ronal NO-synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) have been recognized in the gastroin- testinal tract. The protective properties of the NO derived from constitutive NO synthases (eNOS and nNOS) have already been well established. Less clear is the role assigned to iNOS [1]. Constitutively produced NO is believed to be an important component of mucosal defence mechanisms, primarily because it increases mucosal blood flow. NO is an 1590-8658/$30 © 2008 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2008.06.011