NDLI: Diabetes Recovery By Age-Dependent Conversion of Pancreatic δ-CellsInto Insulin Producers

Content Provider	PubMed Central
Author	Chera, Simona Baronnier, Delphine Ghila, Luiza Valentina, Cigliola Jensen, Jan N. Gu, Guoqiang Furuyama, Kenichiro Thorel, Fabrizio Gribble, Fiona M. Reimann, Frank Herrera, Pedro L.
Abstract	Total or near-total loss of insulin-producing β-cells is a situation foundin diabetes (Type 1, T1D) 1,2 . Restoration of insulin production in T1D isthus a major medical challenge. We previously observed in mice in which β-cells arecompletely ablated that the pancreas reconstitutes new insulin-producing cells in absenceof autoimmunity 3 . The process involvesthe contribution of islet non-β-cells; specifically, glucagon-producingα-cells begin producing insulin by a process of reprogramming(transdifferentiation) without proliferation 3 . Here we studied the influence of age on β-cell reconstitutionfrom heterologous islet cells after near-total β-cell loss. We found thatsenescence does not alter α-cell plasticity: α-cells can reprogram toproduce insulin from puberty through adulthood, and also in aged individuals, even along-time after β-cell loss. In contrast, prior to puberty there is no detectableα-cell conversion, although β-cell reconstitution after injury is moreefficient, always leading to diabetes recovery; it occurs through a newly discoveredmechanism: the spontaneous en masse reprogramming of somatostatin-producingδ-cells. The younglings display “somatostatin-to-insulin”δ-cell conversion, involving de-differentiation, proliferation and re-expression ofislet developmental regulators. This juvenile adaptability relies, at least in part, uponcombined action of FoxO1 and downstream effectors. Restoration of insulin producing-cellsfrom non-β-cell origins is thus enabled throughout life via δ- orα-cell spontaneous reprogramming. A landscape with multiple intra-islet cellinterconversion events is emerging, thus offering new perspectives.
Related Links	http://dx.doi.org/10.1038/nature13633
Ending Page	507
Page Count	5
Starting Page	503
File Format	PDF
ISSN	00280836
e-ISSN	14764687
Journal	Nature
Issue Number	7523
Volume Number	514
Language	English
Publisher Date	2014-08-01
Access Restriction	Open
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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