Neurons and insulin-producing pancreatic beta-cells share multiple common features although they arise from different germ layers 1. In analogy to neurons, beta-cells release insulin by membrane depolarization reminiscent of synaptic neurotransmitter release in neurons and produce the neurotransmitter gamma aminobutyric acid (GABA) in synaptic-like vesicles. Although expression of many individual genes has been shown in neurons and beta-cells, an estimation of the total amount of genes commonly expressed in these cell types has just been addressed recently 2, 3. In a genome-wide mRNA expression scan, profiles of human and rodent beta-cells were compared to non-beta-cell tissues to find genes selectively expressed in beta-cells 2. Interestingly, 15% of these conserved beta-cell markers were also expressed in neuronal tissue coding for proteins involved in neurotransmitter transport, synaptic vesicle formation and brain development 2. To explain why ectodermal-derived neurons and endodermal-derived beta-cells share many common features, Arntfield and van der Kooy have recently speculated that beta-cells may have “borrowed from the brain”, i.e. their ancestors have deployed parts of the neuronal developmental program thereby creating an example of convergent evolution 1. This idea is consistent with the fact that multiple transcription factors are expressed in the neuronal and the pancreatic endocrine lineage including Neurogenin 3 (Ngn3) and NeuroD, both essential for brain and pancreas development. Arntfield et al. have further suggested that the evolution of (modern) beta-cells may have resulted from stochastic effects, i.e. mutation, activating neuronal master transcription factors in gut cells 1. However it remains unclarified which cell type may have first adopted the neuronal program, i.e. a more unspecified gut cell or a pre-differentiated endocrine cell. Recently it has been suggested that beta-cell progenitors co-opt the neural program rather late during their differentiation based on observations on the level of epigenetics 3. Interestingly, neuronal genes are still repressed in multipotent pancreatic progenitors that can give rise to exo- or endocrine tissue suggesting that an activation of neuronal gene activity occured later in the endocrine lineage 3. This would indicate that a pre-differentiated multipotent pancreatic progenitor adopted the neuronal program rather than a more unspecified cell. The notion that neurons and beta-cells are similar has stimulated scientists to transfer principles from neurobiology to understand beta-cell function and to find drugs to support beta-cell function under stress conditions as observed in type 2 diabetes mellitus. For example, screening of a chemical library for neurogenic activators has recently led to the identification of a potent inducer of NeuroD, supporting insulin production in pancreatic beta-cells 4. Moreover, known neuroprotective mechanisms may also be essential in beta-cells as observed in the case of the Parkinson-related antioxidant protein DJ-1 5. DJ-1 preserves mitochondrial integrity in dopaminergic neurons that are vulnerable to reactive oxygen species. In analogy to neurons, DJ-1 also protects the mitochondrial function of beta-cells suggesting that beta-cells and neurons share similar oxidative stress defence mechanisms. Thus, the study of common principles in neurons and beta-cells may provide a basis for prevention and treatment of diabetes mellitus and neurodegenerative diseases.
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