AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation

Entezari M., Hashemi D., Taheriazam A., Zabolian A., Mohammadi S., Fakhri F., ...More

Biomedicine and Pharmacotherapy, vol.146, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 146
  • Publication Date: 2022
  • Doi Number: 10.1016/j.biopha.2021.112563
  • Journal Name: Biomedicine and Pharmacotherapy
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: Diabetic patients, Insulin resistance, Glucose metabolism, Diabetic complication, Clinical application, PANCREATIC BETA-CELLS, INHIBITS HEPATIC GLUCONEOGENESIS, INCREASES GLYCOGEN-SYNTHESIS, HIGH-GLUCOSE, ACTIVATING AMPK, MITOCHONDRIAL DYSFUNCTION, NEGATIVE REGULATION, INDUCED AUTOPHAGY, OXIDATIVE STRESS, SKELETAL-MUSCLE
  • Kayseri University Affiliated: No

Abstract

© 2021Diabetes mellitus (DM) is considered as a main challenge in both developing and developed countries, as lifestyle has changed and its management seems to be vital. Type I and type II diabetes are the main kinds and they result in hyperglycemia in patients and related complications. The gene expression alteration can lead to development of DM and related complications. The AMP-activated protein kinase (AMPK) is an energy sensor with aberrant expression in various diseases including cancer, cardiovascular diseases and DM. The present review focuses on understanding AMPK role in DM. Inducing AMPK signaling promotes glucose in DM that is of importance for ameliorating hyperglycemia. Further investigation reveals the role of AMPK signaling in enhancing insulin sensitivity for treatment of diabetic patients. Furthermore, AMPK upregulation inhibits stress and cell death in β cells that is of importance for preventing type I diabetes development. The clinical studies on diabetic patients have shown the role of AMPK signaling in improving diabetic complications such as brain disorders. Furthermore, AMPK can improve neuropathy, nephropathy, liver diseases and reproductive alterations occurring during DM. For exerting such protective impacts, AMPK signaling interacts with other molecular pathways such as PGC-1α, PI3K/Akt, NOX4 and NF-κB among others. Therefore, providing therapeutics based on AMPK targeting can be beneficial for amelioration of DM.