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

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

  • Biomed Pharmacother. 2022 Feb:146:112563. doi: 10.1016/j.biopha.2021.112563.
Maliheh Entezari 1,  Danial Hashemi 2,  Afshin Taheriazam 3,  Amirhossein Zabolian 4,  Shima Mohammadi 5,  Farima Fakhri 5,  Mehrdad Hashemi 6,  Kiavash Hushmandi 7,  Milad Ashrafizadeh 8,  Ali Zarrabi 9,  Yavuz Nuri Ertas 10,  Sepideh Mirzaei 11,  Saeed Samarghandian 12
Affiliations

Affiliations

  • 1 Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  • 2 Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  • 3 Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
  • 4 Department of Orthopedics, School of Medicine, 5th Azar Hospital, Golestan University of Medical Sciences, Golestan, Iran.
  • 5 Kerman University of Medical Sciences, Kerman 7616913555, Iran.
  • 6 Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 7 Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonosis, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  • 8 Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla 34956, Istanbul, Turkey; Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, Turkey.
  • 9 Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer 34396, Istanbul, Turkey.
  • 10 Department of Biomedical Engineering, Erciyes University, Kayseri 38039, Turkey; ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri 38039, Turkey.
  • 11 Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran. Electronic address: [email protected].
  • 12 Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran. Electronic address: [email protected].
PMID: 35062059 DOI: 10.1016/j.biopha.2021.112563
Abstract

Diabetes 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.

Keywords

Clinical application; Diabetic complication; Diabetic patients; Glucose metabolism; Insulin resistance.

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