Abstract
G protein-coupled receptors (GPCRs) constitute the largest superfamily of integral membrane protein receptors. As signal detectors, the several 100 known GPCRs are responsible for sensing the plethora of endogenous ligands that are critical for the functioning of our endocrine system. Although GPCRs are typically considered as detectors for first messengers in classical signal transduction pathways, they seldom operate in isolation in complex biological systems. Intercellular communication between identical or different cell types is often mediated by autocrine or paracrine signals that are generated upon activation of specific GPCRs. In the context of energy homeostasis, the distinct complement of GPCRs in each cell type bridges the autocrine and paracrine communication within an organ, and the various downstream signaling mechanisms regulated by GPCRs can be integrated in a cell to produce an ultimate output. GPCRs thus act as gatekeepers that coordinate and fine-tune a response. By examining the role of GPCRs in activating and receiving autocrine and paracrine signals, one may have a better understanding of endocrine diseases that are associated with GPCR mutations, thereby providing new insights for treatment regimes.
Highlights
To maintain homeostasis in humans, a wide array of extracellular factors is required to harmonize physiological activities between various organs and tissues
It is known that G protein-coupled receptors (GPCRs) participate in almost every process in the regulation of energy homeostasis as well as other physiological processes that are not mentioned in this review
Due to the pleiotropic property of many GPCR ligands, the diversity of GPCRs and their subtypes, and the potential involvement of multiple intracellular signaling pathways and crosstalks, it is rather difficult to distinguish the physiological roles of autocrine and paracrine factors in a tissue
Summary
To maintain homeostasis in humans, a wide array of extracellular factors is required to harmonize physiological activities between various organs and tissues. The GCPRs expressed in the pancreatic islet receive circulatory signals and exert their functions on hormone-secreting cells, initiating the autocrine and/or paracrine regulations between pancreatic cells. The GPCRs exert their functions on hormone-secreting cells via autocrine and/or paracrine regulations.
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