Effects of Roflumilast on Glycaemic Control, Insulin Secretion, Lipid Profile and Pancreatic Histology in Streptozotocin-Induced Diabetic Wistar Rats
Echa Raphael Akpe *
Department of Chemical Pathology, School of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
M. K. Dallatu
Department of Chemical Pathology, School of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
Wali Usman
Department of Chemical Pathology, School of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
A. S. Mainasara
Department of Chemical Pathology and Immunology, College of Health Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
J. M. Bunza
Department of Chemical Pathology, School of Medical Laboratory Science and One Health Institute, Usmanu Danfodiyo University, Sokoto, Nigeria.
Albashir Tahir
Department of Pharmacology, Faculty of Basic Medical Sciences, Sa'adu Zungur University, Bauchi State, Nigeria.
Bello, Miftahu
Department of Chemical Pathology, School of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
Muhammed Danjuma
Department of Chemical Pathology, School of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Background: Diabetes mellitus (DM) is a progressive metabolic disorder characterised by persistent hyperglycaemia, impaired β-cell function, chronic inflammation and oxidative stress. Current antidiabetic therapies improve glycaemic status but may not fully address inflammatory and oxidative processes involved in disease progression. Roflumilast, a selective phosphodiesterase-4 (PDE4) inhibitor, increases intracellular cyclic adenosine monophosphate (cAMP) and suppresses pro-inflammatory mediators; however, its effects in streptozotocin (STZ)-induced diabetic Wistar rats require further characterisation.
Objective: This study evaluated the effects of roflumilast, alone and combined with metformin, on glycaemic control, plasma insulin, lipid profile and pancreatic histology in STZ-induced diabetic Wistar rats.
Methods: Thirty adult male Wistar rats were assigned to five groups (n = 6): non-diabetic control (NDC), diabetic control (DC), metformin 100 mg/kg/day (MET), roflumilast 1 mg/kg/day (ROF) and ROF+MET. Diabetes was induced using a single intraperitoneal STZ injection (80 mg/kg). Treatments were administered orally for 21 days. Fasting blood glucose (FBG), plasma insulin and lipid profile were measured, and pancreatic tissue was examined using haematoxylin and eosin staining.
Results: STZ induced sustained hyperglycaemia and markedly reduced plasma insulin. ROF monotherapy significantly reduced FBG and improved plasma insulin (p < 0.001). ROF+MET produced the greatest glycaemic improvement, with Day-21 FBG statistically comparable to NDC (p = 0.364 vs NDC). ROF also reduced total cholesterol, triglycerides and LDL cholesterol, whereas HDL-cholesterol was unchanged across groups. Histology showed severe islet degeneration in untreated diabetic controls, while ROF and ROF+MET showed near-normal islet morphology.
Conclusion: Roflumilast improved glycaemic, insulin, lipid and pancreatic histological outcomes in STZ-induced diabetic rats, with the combination treatment showing the greatest overall effect.
Keywords: Roflumilast, diabetes mellitus, glycaemic control, insulin secretion, lipid profile, pancreatic histology, Wistar rats