Metabolic intervention by low carbohydrate diet suppresses the onset and progression of neuroendocrine tumors.
Yu ChenTatsuki YamamotoYura TakahashiTomoka MoroTomoko TajimaYukiko SakaguchiNaoaki SakataAkihiko YokoyamaSusumu HijiokaAkane SadaYuko TabataRieko OhkiPublished in: Cell death & disease (2023)
Insulin signaling often plays a role in the regulation of cancer, including tumor initiation, progression, and response to treatment. In addition, the insulin-regulated PI3K-Akt-mTOR pathway plays an important role in the regulation of islet cell proliferation, and this pathway is hyperactivated in human non-functional pancreatic neuroendocrine tumors (PanNETs). We, therefore, investigated the effect of a very low carbohydrate diet (ketogenic diet) on a mouse model that develops non-functional PanNETs to ask how reduced PI3K-Akt-mTOR signaling might affect the development and progression of non-functional PanNET. We found that this dietary intervention resulted in lower PI3K-Akt-mTOR signaling in islet cells and a significant reduction in PanNET formation and progression. We also found that this treatment had a significant effect on the suppression of pituitary NET development. Furthermore, we found that non-functional PanNET patients with lower blood glucose levels tend to have a better prognosis than patients with higher blood glucose levels. This preclinical study shows that a dietary intervention that results in lower serum insulin levels leads to lower insulin signals within the neuroendocrine cells and has a striking suppressive effect on the development and progression of both pancreatic and pituitary NETs.
Keyphrases
- blood glucose
- glycemic control
- neuroendocrine tumors
- type diabetes
- randomized controlled trial
- weight loss
- induced apoptosis
- cell proliferation
- physical activity
- mouse model
- endothelial cells
- cell cycle arrest
- blood pressure
- stem cells
- signaling pathway
- squamous cell carcinoma
- transcription factor
- insulin resistance
- oxidative stress
- cell death
- mesenchymal stem cells
- adipose tissue
- endoplasmic reticulum stress
- replacement therapy