Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes

被引：274

作者：

Cheng, Chia-Wei ^{[1
,6
]}

Villani, Valentina ^{[2
]}

Buono, Roberta ^{[1
,5
]}

Wei, Min ^{[1
]}

Kumar, Sanjeev ^{[4
]}

Yilmaz, Omer H. ^{[6
]}

Cohen, Pinchas ^{[1
]}

Sneddon, Julie B. ^{[3
]}

Perin, Laura ^{[2
]}

Longo, Valter D. ^{[1
,4
,5
]}

机构：

[1] Univ Southern Calif, Dept Biol Sci, Sch Gerontol, Longev Inst, 3715 McClintock Ave, Los Angeles, CA 90089 USA

[2] Univ Southern Calif, GOFARR Lab Organ Regenerat Res & Cell Therapeut, Childrens Hosp Los Angeles, Div Urol,Saban Res Inst, Los Angeles, CA 90027 USA

[3] Univ Calif San Francisco, Ctr Diabet, 513 Parnassus Ave, San Francisco, CA 94143 USA

[4] Univ Southern Calif, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Keck Sch Med, Los Angeles, CA 90027 USA

[5] IFOM FIRC Inst Mol Oncol, Via Adamello 16, I-20139 Milan, Italy

[6] MIT, Koch Inst, 500 Main St, Cambridge, MA 02139 USA

来源：

CELL | 2017年 / 168卷 / 05期

关键词：

STEM-CELLS; INSULIN-RESISTANCE; GLUCOSE; DEDIFFERENTIATION; PROGENITORS; TYPE-1; MICE; MASS; PROLIFERATION; MECHANISMS;

D O I：

10.1016/j.cell.2017.01.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Stem-cell-based therapies can potentially reverse organ dysfunction and diseases, but the removal of impaired tissue and activation of a program leading to organ regeneration pose major challenges. In mice, a 4-day fasting mimicking diet (FMD) induces a stepwise expression of Sox17 and Pdx-1, followed by Ngn3-driven generation of insulin-producing b cells, resembling that observed during pancreatic development. FMD cycles restore insulin secretion and glucose homeostasis in both type 2 and type 1 diabetes mouse models. In human type 1 diabetes pancreatic islets, fasting conditions reduce PKA and mTOR activity and induce Sox2 and Ngn3 expression and insulin production. The effects of the FMD are reversed by IGF-1 treatment and recapitulated by PKA and mTOR inhibition. These results indicate that a FMD promotes the reprogramming of pancreatic cells to restore insulin generation in islets from T1D patients and reverse both T1D and T2D phenotypes in mouse models.

引用

页码：775 / +

页数：26

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