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Generation of functional beta-cell mass, searching for the best way to cure diabetes

Dólleman, S.C (2010) Generation of functional beta-cell mass, searching for the best way to cure diabetes. Bachelor's Thesis, Biology.

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Abstract

Diabetes is becoming a global epidemic. Because the main therapeutic actions have many side effects it is necessary to develop new sources of insulin-producing β-cells. Induction of β-cell mass could be achieved via proliferation of preexisting β-cells or generation of new β-cells out of progenitor cells. To purchase, proliferation of preexisting β-cells, activation of transcription factors E2F and Cdk4, or activation of CRF receptor 1, could achieve this goal. Transcription factor E2F in co-infection with anti-apoptotic growth factor Akt and CRFR1 in a glucose-dependent manner. Also generation of new β-cells out of progenitor cells could be achieved via activation of transcription factors. From ductal cells to β-cell and α- to β-cell the transcription factors INSM1 and Pax4 are used, respectively. INSM1 in combination with islet transcription factor NeuroD1 and Pdx-1. Stimulation of the incretin hormone GLP-1 is another way to achieve ductal to β-cell differentiation. The experiments show great opportunities for new kinds of diabetes treatment. Nowadays the GLP-1 analog Exendin4 is a treatment with great outcomes in experiments with rodents but is not as operative in humans to induce β-cell proliferation. This phenomenon could be due to ageing of β-cells or difference in species. Proliferation of β-cells seems to decline with age. The decline in β-cell proliferation with age correlates with increased expression of the cell cycle regulator p16Ink4a in islet cells. In contrast, compared islet transplantation of young and adult donors do not show any significance difference in β-cell replication in response to hyperglycemia. However, older mice with a more limited regeneration capacity would serve as a better model for assessing therapies for humans.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:31
Last Modified: 15 Feb 2018 07:31
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/9151

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