Table 1.

Similarities between neurons and beta-cells as described by Arntfield et. al [22]. Adapted with permission from John Wiley and Sons, Inc.

Category	Similarity	Description
Physiology & function	APUD phenotype & paraneuron concept	All endocrine cells have the ability to take up and decarboxylate amine precursors, as well as produce polypeptide hormones [23], features that they share with neurons [24].
	Neurotransmitters	β-Cells synthesise glutamate and use it for intracellular signalling in glucose-responsive insulin secretion [25].
	Neurotransmitter assembly proteins	β-Cells express glutamic acid decarboxylase, an enzyme found in gamma aminobutyric acid (GABA)-secreting neurons but not other cell types [26].
	Neurotransmitter receptors	β-Cells contain glutamate receptors, which are mainly found in the central nervous system [27].
	Secretory granules & microvesicles	β-Cells store insulin in secretory granules that are secreted from synaptic-like microvesicles [26].
	Action potentials	Pancreatic β-cells are capable of generating action potentials similar to those used by neurons to transmit signals along their axons. These action potentials may cause the release of insulin from b-cells in a manner akin to the release of neurotransmitters from neurons [28].
	Glucose response	Neurons in the hypothalamus can sense blood glucose levels and are stimulated by changes in the same way β-cells are [29].
	Schwann cells	Islets are surrounded and highly penetrated by Schwann cells, the major glial cell of the peripheral nervous system [30]. These Schwann cells may be functioning as support cells for both the islets and innervating neurons [30].
	Cell migration	The migration of pancreatic precursors into the surrounding mesenchyme has been shown to be dependent on the axon guidance protein, netrin-1 [31].
	Adhesion molecules	Endocrine cells of adult mammalian islets associate partially by the expression of neural cell adhesion molecule (NCAM) [32].
Gene expression	Global gene expression	β-Cells are more similar in global mRNA expression and chromatin methylation pattern to neurons than any other cell type, including pancreatic acinar cells [33].
	Sodium channels	Islet cells express the alpha-1 subunit sodium channel mRNA which is primarily expressed in the brain [34].
	Neurofilaments	Dissociated b-cells have been found to synthesise neurofilaments in vitro which may be recapitulating their developmental migration [26].
	REST expression	β-Cells lack expression of repressor element 1 silencing transcription factor (REST) which is expressed in non-neuronal cells and suppresses the neuronal phenotype [35].
	Insulin & other pancreatic endocrine hormones	Insulin, glucagon and ghrelin are expressed in the brain during development and in adulthood [36, 37].
	Glucosetransporters	The β-cell specific glucose transporter, Glut-2, is expressed in certain regions of the brain, including the hypothalamus, one of the sites of insulin action [38].
	Isl-1	The homeodomain protein Isl-1 is expressed in mature pancreatic endocrine cells, calcitonin-producing thyroid cells and neurons of the peripheral and central nervous systems [39].
Development	Pax-6	Pax-6 is involved in development of a-cells of the pancreas and proper insulin secretion from b-cells [40], as well as neurogenesis in the developing central nervous system [41].
	Nkx6.1	Nkx6.1 is a transcription factor involved in the formation of b-cells in the pancreas [40] as well as maturation and migration of hindbrain motor neurons [42].
	Notch	Notch is a transmembrane signalling protein that has been implicated in maintaining pancreatic precursors in a proliferative state, as well as influencing cell fate decisions [40]. Notch has been shown to have similar functions in the developing nervous system [41].
	Neurogenin	The transcription factor neurogenin-3 is repressed by Notch and when activated it contributes to specification of endocrine cells in the pancreas [40]. Notch may also repress neurogenin-1 and 2 which are involved in the specification of neurons from neural progenitors [41].
	HB9	HB9 is expressed in the embryonic gut and initiates formation of the pancreatic bud and is later expressed in mature b-cells [40]. BHB9 is also expressed in embryonic and adult motor neurons [43].
	PDXI	The pancreatic specific transcription factor PDXI is turned on in the brain during development [44].