التفاصيل البيبلوغرافية
| العنوان: |
Pharmacological conversion of gut epithelial cells into insulin-producing cells lowers glycemia in diabetic animals |
| المؤلفون: |
Du, Wen, Wang, Junqiang, Kuo, Taiyi, Wang, Liheng, McKimpson, Wendy M, Son, Jinsook, Watanabe, Hitoshi, Kitamoto, Takumi, Lee, Yun-Kyoung, Creusot, Remi J, Ratner, Lloyd E, McCune, Kasi, Chen, Ya-Wen, Grubbs, Brendan H, Thornton, Matthew E, Fan, Jason, Sultana, Nishat, Diaz, Bryan S, Balasubramanian, Iyshwarya, Gao, Nan, Belvedere, Sandro, Accili, Domenico |
| المصدر: |
Journal of Clinical Investigation, vol 132, iss 24 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2022 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Diabetes, Autoimmune Disease, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Humans, Mice, Animals, Forkhead Box Protein O1, Forkhead Transcription Factors, Inbred NOD, Insulin-Secreting Cells, Insulin, Diabetes Mellitus, Beta cells, Endocrinology, Medical and Health Sciences, Immunology |
| الوصف: |
As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt3hp5q86p; https://escholarship.org/uc/item/3hp5q86pTest |
| الإتاحة: |
https://escholarship.org/uc/item/3hp5q86pTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.D3EC9950 |
| قاعدة البيانات: |
BASE |
