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Increased beta cell mass in mice where FGFR1c is expressed in alpha cells
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Helena Edlund)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Helena Edlund)
(English)Manuscript (preprint) (Other academic)
Abstract [en]

FGFR1 is selectively expressed in adult b- but not a-cells and signalling via FGFR1 is crucial for adult b-cell function. When signalling via the FGFR1c pathway is perturbed in b-cells of genetically modified “FRID1” mice, they develop late-onset diabetes and, remarkably, exhibit the three major b-cell defects observed in human type 2 diabetics; i) Impaired glucose sensing due to perturbed b-cell expression of Glut2; ii) increased proinsulin content in b-cells due to drastically reduced production of PC1/3; the enzyme essential for the generation of mature, biologically active insulin from its precursor form, proinsulin;  iii) a reduced number of b-cells, as compared with matched controls, due to reduced ability of b-cells to divide after birth. Furthermore, the transcription factor IPF1/PDX1, which controls several key functional properties of b-cells and is linked to diabetes in man, is required to maintain FGF-signalling in b-cells. Together these results point to a crucial role for FGFR1-signalling in controlling the generation of normal numbers of b-cells and glucose homeostasis. To further investigate the mechanism by which FGFR1 signalling influences key b-cell properties as well as b-mass we mis-expressed of FGFR1c in a-cells using the glucagon promoter.

Keyword [en]
diabetes pancreas fgf
National Category
Developmental Biology
Research subject
Developmental Neurosciences
URN: urn:nbn:se:umu:diva-25794OAI: diva2:233892
In vivo and in vitro approaches to induce beta cells from stem and progenitor cells
Available from: 2009-09-03 Created: 2009-09-03 Last updated: 2010-01-14Bibliographically approved
In thesis
1. In vivo and in vitro approaches to induce beta cells from stem and progenitor cells
Open this publication in new window or tab >>In vivo and in vitro approaches to induce beta cells from stem and progenitor cells
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diabetes or diabetes mellitus which is the correct medical term is a medical condition were the affected person lack the ability to regulate his or her blood glucose levels. This inability is directly due to the fact that the insulin producing cells, residing in the pancreas, can’t meet the body’s demand for insulin. It is estimated that close to 200 million people are suffering from diabetes today and this number is predicted to double within 20 years. Of the approximately 200 million people suffering from diabetes today approximately 20 million are in dependent on daily injections of insulin. Being dependent on exogenous insulin is not only an inconvenience it also increase the risk for several medical complications such as stroke, heart disorders, kidney failure, retinopathy, atherosclerosis and impaired wound healing. The major risk factor for all these complications is long periods of high blood sugar levels that is damaging to thin blood vessels and nerves.  Even in the best of situations the blood sugar levels of a diabetic with need for daily insulin injections can never be as well controlled as in a healthy individual.

Increased understanding in the developmental processes behind the formation of the pancreas, and more specifically the insulin producing β-cells could result in new treatments for diabetics. By imitating the in vivo conditions generating pancreatic development scientist are now able to induce embryonic stem cells to differentiate into pancreatic progenitors as well as insulin producing β-cells in vitro. These in vitro generated pancreatic cells might in the future serve as a donor source for transplantations, thereby restoring the insulin producing capability of diabetic patients. An alternative approach to restore insulin production in diabetics is to influence cells in the pancreas to generate more insulin producing cells. To successfully achieve this, what cell types have the capacity to generate β-cells needs to be appreciated.

In this thesis papers concerning in vitro differentiating of embryonic stem cells towards a pancreatic fate as well as in vivo studies in basic pancreas development are presented and discussed.

92 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1287
pancreas, stem cell, progenitor, beta cell, in vitro
National Category
Medical Genetics
Research subject
Molecular Medicine
urn:nbn:se:umu:diva-25813 (URN)978-91-7268-846-3 (ISBN)
Umeå centrum för molekylär medicin (UCMM), 90185, Umeå
Public defence
2009-09-25, Major Groove, Byggnad 6L, Umeå, 13:00 (English)
Available from: 2009-09-09 Created: 2009-09-03 Last updated: 2010-01-18Bibliographically approved

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