Gut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis
Abstrak
Abstract Diabetes is known to increase the risk of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Here we treat male STAM (STelic Animal Model) mice, which develop diabetes, NASH and HCC associated with dysbiosis upon low-dose streptozotocin and high-fat diet (HFD), with insulin or phlorizin. Although both treatments ameliorate hyperglycemia and NASH, insulin treatment alone lead to suppression of HCC accompanied by improvement of dysbiosis and restoration of antimicrobial peptide production. There are some similarities in changes of microflora from insulin-treated patients comorbid with diabetes and NASH. Insulin treatment, however, fails to suppress HCC in the male STAM mice lacking insulin receptor specifically in intestinal epithelial cells (ieIRKO), which show dysbiosis and impaired gut barrier function. Furthermore, male ieIRKO mice are prone to develop HCC merely on HFD. These data suggest that impaired gut insulin signaling increases the risk of HCC, which can be countered by restoration of insulin action in diabetes.
Topik & Kata Kunci
Penulis (25)
Kotaro Soeda
Takayoshi Sasako
Kenichiro Enooku
Naoto Kubota
Naoki Kobayashi
Yoshiko Matsumoto Ikushima
Motoharu Awazawa
Ryotaro Bouchi
Gotaro Toda
Tomoharu Yamada
Takuma Nakatsuka
Ryosuke Tateishi
Miwako Kakiuchi
Shogo Yamamoto
Kenji Tatsuno
Koji Atarashi
Wataru Suda
Kenya Honda
Hiroyuki Aburatani
Toshimasa Yamauchi
Mitsuhiro Fujishiro
Tetsuo Noda
Kazuhiko Koike
Takashi Kadowaki
Kohjiro Ueki
Akses Cepat
- Tahun Terbit
- 2023
- Sumber Database
- DOAJ
- DOI
- 10.1038/s41467-023-42334-y
- Akses
- Open Access ✓