Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell

Menegaz, Danusa; Hagan, D. Walker; Almaça, Joana; Cianciaruso, Chiara; Rodriguez-Diaz, Rayner; Molina, Judith; Dolan, Robert; Becker, Matthew W.; Schwalie, Petra; Nano, Rita; Lebreton, Fanny; Chen, Kang; Sah, Rajan; Gaisano, Herbert Y.; Berggren, Per Olof; Baekkeskov, Steinunn; Caicedo, Alejandro; Phelps, Edward A.

doi:10.1038/s42255-019-0135-7

Cited by 66 publications

(79 citation statements)

References 110 publications

(174 reference statements)

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“…REG1A is associated with β cell regeneration ( 64 ). GLS hydrolyses glutamine to glutamate, which is a key regulator of α cell secretion ( 65 ) and an immediate precursor to γ-aminobutyric acid (GABA) secreted from β cells ( 66 ).…”

Section: Resultsmentioning

confidence: 99%

GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells

Saikia¹,

Holter²,

Donahue³

et al. 2021

JCI Insight

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Section: Resultsmentioning

confidence: 99%

GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells

Saikia¹,

Holter²,

Donahue³

et al. 2021

JCI Insight

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“…Finally, glutamate is also produced by the beta cell itself during glucose metabolism and this endogenous glutamate influences incretin-induced insulin secretion [ 20 ]. Glutamate is also the substrate for the synthesis of GABA, which is an important paracrine signal released by the beta cell that inhibits glucagon-release from alpha cells [ 21 , 22 ].…”

Section: Factors Released By the Alpha Cellmentioning

confidence: 99%

Alpha cell regulation of beta cell function

2020

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The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types. The two most abundant and prominent endocrine cell types, the beta and the alpha cells, are essential for the maintenance of blood glucose homeostasis. While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. Under physiological conditions, these two cell types affect each other in a paracrine manner. While the release products of the beta cell inhibit alpha cell function, the alpha cell releases factors that are stimulatory for beta cell function and increase glucose-stimulated insulin secretion. The aim of this review is to provide a comprehensive overview of recent research into the regulation of beta cell function by alpha cells, focusing on the effect of alpha cell-secreted factors, such as glucagon and acetylcholine. The consequences of differences in islet architecture between species on the interplay between alpha and beta cells is also discussed. Finally, we give a perspective on the possibility of using an in vivo imaging approach to study the interactions between human alpha and beta cells under in vivo conditions.

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“…GABA (gamma-aminobutyric acid) is also released from HEK293 cells via VSOR in an LRRC8D- and LRRC8E-dependent manner ( Lutter et al, 2017 ). LRRC8A deletion and silencing abolished GABA release from mouse and human pancreatic β cells ( Menegaz et al, 2019 ). Since GABA has strong protective and regenerative effects on β cells ( Fiorina, 2013 ), it is likely that an impairment of VSOR-mediated GABA release may participate in etiology of diabetes mellitus.…”

Section: Roles Of Vsor/vrac In Release Of Organic Signals For Cell Dementioning

confidence: 99%

“…Since GABA has strong protective and regenerative effects on β cells ( Fiorina, 2013 ), it is likely that an impairment of VSOR-mediated GABA release may participate in etiology of diabetes mellitus. Actually, Type-1 and -2 diabetic islets of human patients were shown to exhibit disrupted secretion of GABA ( Menegaz et al, 2019 ).…”

Section: Roles Of Vsor/vrac In Release Of Organic Signals For Cell Dementioning

confidence: 99%

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 1: Roles of VSOR/VRAC in Cell Volume Regulation, Release of Double-Edged Signals and Apoptotic/Necrotic Cell Death

Okada

Sabirov

Sato-Numata

et al. 2021

Front. Cell Dev. Biol.

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Cell volume regulation (CVR) is essential for survival and functions of animal cells. Actually, normotonic cell shrinkage and swelling are coupled to apoptotic and necrotic cell death and thus called the apoptotic volume decrease (AVD) and the necrotic volume increase (NVI), respectively. A number of ubiquitously expressed anion and cation channels are involved not only in CVD but also in cell death induction. This series of review articles address the question how cell death is induced or protected with using ubiquitously expressed ion channels such as swelling-activated anion channels, acid-activated anion channels and several types of TRP cation channels including TRPM2 and TRPM7. The Part 1 focuses on the roles of the volume-sensitive outwardly rectifying anion channels (VSOR), also called the volume-regulated anion channel (VRAC), which is activated by cell swelling or reactive oxygen species (ROS) in a manner dependent on intracellular ATP. First we describe phenotypical properties, the molecular identity, and physical pore dimensions of VSOR/VRAC. Second, we highlight the roles of VSOR/VRAC in the release of organic signaling molecules, such as glutamate, glutathione, ATP and cGAMP, that play roles as double-edged swords in cell survival. Third, we discuss how VSOR/VRAC is involved in CVR and cell volume dysregulation as well as in the induction of or protection from apoptosis, necrosis and regulated necrosis under pathophysiological conditions.

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Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell

Cited by 66 publications

References 110 publications

GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells

GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells

Alpha cell regulation of beta cell function

Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 1: Roles of VSOR/VRAC in Cell Volume Regulation, Release of Double-Edged Signals and Apoptotic/Necrotic Cell Death

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