β-Cell Autophagy Pathway and Endoplasmic Reticulum Stress Regulating-Role of Liposomal Curcumin in Experimental Diabetes Mellitus: A Molecular and Morphometric Study
Safaa I. Khater,
Mohamed F. Dowidar,
Aya E. Abdel-Aziz,
Tarek Khamis,
Naief Dahran,
Leena S. Alqahtani,
Mohamed M. M. Metwally,
Al-Sayed Al-Hady Abd-Elrahamn,
Mohammed Alsieni,
Manal E. Alosaimi,
Maram H. Abduljabbar,
Amany Abdel-Rahman Mohamed
Affiliations
Safaa I. Khater
Department of Biochemistry, Zagazig University, Zagazig 44511, Egypt
Mohamed F. Dowidar
Department of Biochemistry, Zagazig University, Zagazig 44511, Egypt
Aya E. Abdel-Aziz
Department of Biochemistry, Zagazig University, Zagazig 44511, Egypt
Tarek Khamis
Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
Naief Dahran
Department of Anatomy, Faculty of Medicine, University of Jeddah, Jeddah 23218, Saudi Arabia
Leena S. Alqahtani
Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia
Mohamed M. M. Metwally
Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Al-Sayed Al-Hady Abd-Elrahamn
Department of Human Anatomy and Embryology, Port Said University, Port Said 42511, Egypt
Mohammed Alsieni
Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Manal E. Alosaimi
Department of Basic Science, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Maram H. Abduljabbar
Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia
Amany Abdel-Rahman Mohamed
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Background: Autophagy can confer protection to pancreatic β-cells from the harmful effects of metabolic stress by delaying apoptosis. Curcumin (CUR) alleviates oxidative and endoplasmic reticulum (ER) stress, activates autophagy, reduces inflammation, and decreases β-cell damage in type I diabetes. Liposomal CUR (LPs-CUR) has a higher therapeutic value and better pharmacokinetics than CUR. Objectives: We determined LPs-CUR’s ability to alleviate stress, reduce β-cell damage and unraveled the mechanism underlying its protective effect using a streptozotocin (STZ)-induced type I diabetic rat model. Methods: Sprague–Dawley rats were grouped into vehicle control, STZ-diabetic (STZ 65 mg/kg), STZ-diabetic-3-MA (3-methyladenine [3-MA] 10 mg/kg b.wt), STZ. diabetic-LPs-CUR (LPs-CUR 10 mg/kg b.wt), and STZ diabetic-LPs-CUR-3-MA (LPs-CUR 10 mg/kg b.wt; 3-MA 10 mg/kg b.wt). Results: LPs-CUR significantly reduced blood glucose, oxidative stress, and cellular inflammation in the pancreatic tissue (p < 0.001). ER stress-dependent genes included ATF-6, eIF-2, CHOP, JNK, BiP, and XBP LPs-CUR significantly suppressed fold changes, while it upregulated the autophagic markers Beclin-1 and LC3-II. Conclusions: LP-CUR ameliorates β-cell damage by targeting the autophagy pathway with the regulatory miRNAs miR-137 and miR-29b, which functionally abrogates ER stress in β-cells. This study presents a new therapeutic target for managing type I diabetes using miR-137 and miR-29b.
