Single-agent FOXO1 inhibition normalizes glycemia and induces gut β-like cells in streptozotocin-diabetic mice

Lee, Yun-Kyoung; Du, Wen; Nie, Yaohui; Diaz, Bryan; Sultana, Nishat; Kitamoto, Takumi; Leibel, Rudolph L.; Accili, Domenico; Belvedere, Sandro

doi:10.1016/j.molmet.2022.101618

Cited by 4 publications

(1 citation statement)

References 23 publications

(33 reference statements)

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“…We showed that combination treatment with the first‐generation FOXO1 inhibitor, FBT10, and the gamma‐secretase inhibitor, PF‐03084014, has additive effects on gut β‐like cell generation and glucose levels in Akita mice 25 . We also showed a synergistic glucose‐lowering effect by combining another FOXO1 inhibitor, FBT432, with PF‐03084014 in streptozotocin‐treated mice 47 . The effects of treatment on fasting glycemia, intraperitoneal glucose tolerance, glucosuria and ketonuria were remarkable.…”

Section: Foxo1 Inhibitors Lower Glycemia In Insulin‐deficient Diabetesmentioning

confidence: 82%

Diabetes treatment by conversion of gut epithelial cells to insulin‐producing cells

Accili,

Talchai,

Bouchi

et al. 2024

J of Diabetes Invest

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Insulin‐deficient (type 1) diabetes is treated by providing insulin to maintain euglycemia. The current standard of care is a quasi‐closed loop integrating automated insulin delivery with a continuous glucose monitoring sensor. Cell replacement technologies are advancing as an alternative treatment and have been tested as surrogates to cadaveric islets in transplants. In addition, immunomodulatory treatments to delay the onset of type 1 diabetes in high‐risk (stage 2) individuals have gained regulatory approval. We have pioneered a cell conversion approach to restore insulin production through pharmacological conversion of intestinal epithelial cells into insulin‐producing cells. We have advanced this approach along a translational trajectory through the discovery of small molecule forkhead box protein O1 inhibitors. When administered to different rodent models of insulin‐deficient diabetes, these inhibitors have resulted in robust glucose‐lowering responses and generation of insulin‐producing cells in the gut epithelium. We review past work and delineate a path to human clinical trials.

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Section: Foxo1 Inhibitors Lower Glycemia In Insulin‐deficient Diabetesmentioning

confidence: 82%

Diabetes treatment by conversion of gut epithelial cells to insulin‐producing cells

Accili,

Talchai,

Bouchi

et al. 2024

J of Diabetes Invest

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Harnessing gut cells for functional insulin production: Strategies and challenges

Baafi

March

2023

Biotechnology Notes

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The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2–EP4 receptor–AKT signaling in a type 2 diabetes mellitus mouse model

Liang

Wang

2023

Cellular Signalling

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Single-agent FOXO1 inhibition normalizes glycemia and induces gut β-like cells in streptozotocin-diabetic mice

Cited by 4 publications

References 23 publications

Diabetes treatment by conversion of gut epithelial cells to insulin‐producing cells

Diabetes treatment by conversion of gut epithelial cells to insulin‐producing cells

Harnessing gut cells for functional insulin production: Strategies and challenges

The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2–EP4 receptor–AKT signaling in a type 2 diabetes mellitus mouse model

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