The prevalence of diabetes mellitus (DM) continues to increase throughout the world.
In the United States (US) alone, approximately ten percent of the population is diagnosed with DM
and another thirty-five percent of the population is considered to have prediabetes. Yet, current
treatments for DM are limited and can fail to block the progression of multi-organ failure over
time. Wnt1 inducible signaling pathway protein 1 (WISP1), also known as CCN4, is a matricellular
protein that offers exceptional promise to address underlying disease progression and develop
innovative therapies for DM. WISP1 holds an intricate relationship with other primary pathways
of metabolism that include protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP
activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces
cerevisiae) (SIRT1), and mammalian forkhead transcription factors (FoxOs). WISP1
is an exciting prospect to foster vascular as well as neuronal cellular protection and regeneration,
control cellular senescence, block oxidative stress injury, and maintain glucose homeostasis.
However, under some scenarios WISP1 can promote tumorigenesis, lead to obesity progression
with adipocyte hyperplasia, foster fibrotic hepatic disease, and lead to dysregulated inflammation
with the progression of DM. Given these considerations, it is imperative to further elucidate the
complex relationship WISP1 holds with other vital metabolic pathways to successfully develop
WISP1 as a clinically effective target for DM and metabolic disorders.
Keywords: Akt, AMP activated protein kinase (AMPK), autophagy, cancer, CCN4, diabetes mellitus, forkhead transcription
factors, FoxO, inflammation, interleukin 18 (IL-18), mechanistic target of rapamycin (mTOR), oxidative stress, silent mating
type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), sirtuin, stem cells, Wnt1 inducible signaling
pathway protein 1 (WISP1), WISP-1, wingless, Wnt.
open access plus
Centers for Disease Control and Prevention. National Diabetes
Statistics Report 2020. 2020. CS 314227-A:1-30.
Feng M, Jia S. Dual effect of WISP-1 in diverse pathological processes.
Chinese journal of cancer research = Chung-kuo yen cheng
yen chiu 2016; 28(6): 553-60.
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