Title: Why expression of some genes is disallowed in beta-cells
Authors: Quintens, Roel ×
Hendrickx, Nico
Lemaire, Katleen
Schuit, Frans #
Issue Date: Jun-2008
Publisher: Portland Press
Series Title: Biochemical Society Transactions vol:36 pages:300-305
Conference: Pancreatic b-cell: birth, life and death location:London date:3-4 December 2007
Abstract: A differentiated beta-cell results not only from cell-specific gene expression, but also from cell-selective repression of certain housekeeping genes. indeed, to prevent insulin toxicity, beta-cells should handle insulin stores carefully, preventing excicytosis under conditions when circulating insulin is unwanted. Some ubiquitously expressed proteins would significantly jeopardize this safeguard, when allowed to function in beta-cells. This is illustrated by two studied examples. First, low-K-m hexokinases are disallowed as their high affinity for glucose would, when expressed, significantly lower the threshold for glucose-induced beta-cell function and cause hypoglycaemia, as happens in patients with beta-cell tumours. Thus the beta-cell phenotype means not only expression of glucokinase but also absence of low-K-m hexokinases. Secondly, the absence of MCTs (monocarboxylic acid transporters) in beta-cells explains the pyruvate paradox (pyruvate being an excellent substrate for mitochondrial ATP production, yet not stimulating insulin release when added to beta-cells). The relevance of this disallowance is underlined in patients with exercise-induced inappropriate insulin release: these have gain-of-function MCT1 promoter mutations and loss of the pyruvate paradox. By genome-wide ex vivo mRNA expression studies using mouse islets and an extensive panel of other tissues, we have started to identify in a systematic manner other specifically disallowed genes. For each of those, the future challenge is to explore the physiological/pathological relevance and study conditions under which the phenotypically disallowed state in the beta-cell is breached.
ISSN: 0300-5127
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
× corresponding author
# (joint) last author

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