An atlas and functional analysis of G-protein coupled receptors in human islets of Langerhans

Anti-diabetic action of all-trans retinoic acid and the orphan G protein coupled receptor GPRC5C in pancreatic β-cells

“…We have recently shown that two members of the GPRC5 family (GPRC5B and GPRC5C) are highly expressed in both mouse and human islets [9,15]. While activation of GPRC5B leads to reduced β-cell function in terms of a reduced viability and a reduced secretory capacity [9], the functional role of GPRC5C in β-cells has not been investigated to date.…”

“…We recently reported that the membrane-bound G-protein coupled receptor GPRC5C is highly expressed in pancreatic islets [15]. We have now investigated the expression of GPRC5C in human and mouse pancreatic islets and studied the consequences of GPRC5C down-regulation on glucose-stimulated insulin secretion, insulin content, cell proliferation and islet cell viability.…”

Serotonin (5-HT) receptor 2b activation augments glucose-stimulated insulin secretion in human and mouse islets of Langerhans

“…Clinically, 5-HT systems in the central nervous system are targeted by antidepressants and long-term use of antidepressants is associated with an increased type 2 diabetes risk [38,39]. Since beta cells express multiple 5-HT receptors [10,11] and the serotonin transporter (SERT) [40], direct effects on insulin secretion are likely. Indeed, selective serotonin re-uptake inhibitors (SSRIs) inhibit insulin secretion in clonal beta cells [41,42], possibly through an increased 5-HT concentration in the extracellular space.…”

“…Serotonin (5-hydroxytryptamine ) receptors are expressed in rodent islets [6][7][8] and virtually all 5-HT receptors (5-HT 1-7 ) are G protein-coupled with the exception of 5-HT 3 receptors (ligand-gated K + and Na + ion channels) [9]. Recently, microarray and RNA sequencing analyses revealed transcripts of almost all 5-HT receptors in human islets [10,11]. The natural ligand binding to these receptors, 5-HT, is synthesised from the amino acid tryptophan, is a well-established neurotransmitter in the central nervous system and is involved in regulation of mood and behaviour [9].…”

G Protein–Coupled Receptor (GPCR) Expression in Native Cells: “Novel” endoGPCRs as Physiologic Regulators and Therapeutic Targets

“…The receptors include those that interact with endogenous ligands (endoGPCRs); GPCRs regulated by exogenous factors, such as photons of light, odorants, and tastants (chemosensory receptors); and GPCRs that lack known physiologic ligands (termed orphan receptors). It is estimated that among the approximately 800 GPCRs in humans, ∼380 are endoGPCRs, of which about one-third are orphan receptors, even though there have been substantial efforts at deorphanization (Fredriksson et al, 2003;Kroeze et al, 2003;Ozawa et al, 2010;Amisten et al, 2013;Civelli et al, 2013).…”