Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

Cells. 2023 Nov 9;12(22):2595. doi: 10.3390/cells12222595.


Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world and are insidious in onset, chronic in nature, and yield significant disability and death. Current therapies that address nutritional status, weight management, and pharmacological options may delay disability but cannot alter disease course or functional organ loss, such as dementia and degeneration of systemic bodily functions. Underlying these challenges are the onset of aging disorders associated with increased lifespan, telomere dysfunction, and oxidative stress generation that lead to multi-system dysfunction. These significant hurdles point to the urgent need to address underlying disease mechanisms with innovative applications. New treatment strategies involve non-coding RNA pathways with microRNAs (miRNAs) and circular ribonucleic acids (circRNAs), Wnt signaling, and Wnt1 inducible signaling pathway protein 1 (WISP1) that are dependent upon programmed cell death pathways, cellular metabolic pathways with AMP-activated protein kinase (AMPK) and nicotinamide, and growth factor applications. Non-coding RNAs, Wnt signaling, and AMPK are cornerstone mechanisms for overseeing complex metabolic pathways that offer innovative treatment avenues for metabolic disease and DM but will necessitate continued appreciation of the ability of each of these cellular mechanisms to independently and in unison influence clinical outcome.

Keywords: AMP-activated protein kinase (AMPK); Wnt; Wnt1 inducible signaling pathway protein 1 (WISP1); aging; apoptosis; autophagy; erythropoietin; nicotinamide; non-coding RNA; oxidative stress.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Apoptosis / physiology
  • Diabetes Mellitus* / metabolism
  • Humans
  • Metabolic Diseases* / genetics
  • Wnt Signaling Pathway / genetics


  • AMP-Activated Protein Kinases