Release of Endogenous Opioids From Duodenal Enteroendocrine Cells Requires Trpm5

Kokrashvili, Zaza; Rodriguez, Deniliz; Yevshayeva, Valeriya; Zhou, Hang; Margolskee, Robert F.; Mosinger, B

doi:10.1053/j.gastro.2009.02.070

Cited by 77 publications

(71 citation statements)

References 61 publications

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“…Previously, Trpm5 expression was shown on the mRNA level in several β-cell lines and in human and mouse tissues, including taste buds, intestine, and pancreatic islets (13,(17)(18)(19)(20)(21)(22). Here we describe immunostaining of TRPM5 protein in pancreatic islets with a specific antibody (Fig.…”

Section: Resultsmentioning

confidence: 99%

Loss of high-frequency glucose-induced Ca ²⁺ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 ^−/− mice

Colsoul

Schraenen

Lemaire

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Glucose homeostasis is critically dependent on insulin release from pancreatic β-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V m ) and the cytosolic calcium level ([Ca 2+ ] cyt ] cyt ) (1-4). This pattern, consisting of slow waves of depolarized plateaus on which bursts of action potentials are superimposed and separated by electrically silent intervals, plays a critical role in the regulation of insulin secretion. Indeed, in the absence of depolarization, no insulin is released, and the "extent" of electrical activity largely determines the amount of released insulin (1,5 ] cyt ), and the cellular metabolism of the β-cell (1, 6). The increase in [Ca 2+ ] cyt originates from glucoseinduced Ca 2+ influx through voltage-gated L-type Ca 2+ channels and, possibly, Ca 2+ mobilization from intracellular stores, the latter promoted by activation of the phospholipase C system and generation of inositol 1,4,5-trisphosphate (1,7,8). Despite intensive investigation, several aspects of the rhythmic electrical activity of β-cells, such as the origin of the variability in oscillation pattern, remain unclear. Indeed, glucose stimulation can result in highfrequency short bursts, low-frequency long bursts, or a combination of these two patterns, also known as compound bursts (9, 10).In this study we identified TRPM5 as a player in the electrical activity of glucose-stimulated pancreatic β-cells. TRPM5 is one of 28 members of the large transient receptor potential (TRP) superfamily (11-13). TRPM5, and its close homologue TRPM4, are Ca 2+ -activated cation channels that are permeable for monovalent cations, but not divalent cations, with a conductance of approximately 20 to 25 pS (14-16). Using Trpm5−/− mice we show here that this channel promotes high-frequency glucose-induced oscillations in V m and [Ca 2+ ] cyt in pancreatic β-cells. Loss of TRPM5 expression, and high-frequency bursting, is functionally relevant as this leads to reduced glucose-induced insulin release from isolated islets and impaired glucose tolerance. Results and DiscussionExpression of the Trpm5 Gene in Pancreatic β-Cells. Previously, Trpm5 expression was shown on the mRNA level in several β-cell lines and in human and mouse tissues, including taste buds, intestine, and pancreatic islets (13,(17)(18)(19)(20)(21)(22). Here we describe immunostaining of TRPM5 protein in pancreatic islets with a specific antibody (Fig. 1). TRPM5 is colocalized with insulin in WT islets, strongly suggesting expression of TRPM5 in insulin secreting β-cells. Specific staining with the TRPM5 antibody is absent in Trpm5 −/− islets. Quantitative PCR experiments in a purified β-cell sample confirmed expression of Trpm5 in the β-cells. Expression of Trpm5 could also be detected in purified α-cells, although to a lower level compared with β-cells (Fig. S1). Characterization of a Ca2+ Release-Activated Cation Current in Pancreatic Islet Cells. To determine whether TRPM5 is part of the Ca 2+-activated monovalent cation current descri...

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Section: Resultsmentioning

confidence: 99%

Loss of high-frequency glucose-induced Ca ²⁺ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 ^−/− mice

Colsoul

Schraenen

Lemaire

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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184

160

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“…TRPM5 is also expressed in a well defined subset of enteroendocrine cells, the so-called L cells (Kokrashvili et al, 2009). These cells secrete the incretin hormone GLP-1 that, in turn, influences satiety via three mechanisms: 1) it suppresses food consumption; 2) it facilitates gastric emptying, and 3) it promotes insulin release in response to glucose (reviewed in De Silva and Bloom, 2012).…”

Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 99%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Nilius

Szállaśi

2014

Pharmacological Reviews

448

481

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“…TRPM5 immunoreactivity was also seen in other chemosensory organs-the main olfactory epithelium and the vomeronasal organ, hinting at its potential functions in chemosensation (Kaske et al, 2007). Using TRPM5-GFP transgenic and TRPM5(Ϫ/Ϫ) mice, a recent study showed that TRPM5 is expressed in solitary enteroendocrine chemosensory cells in mouse duodenum and may be essential for the release of the endogenous opioids ␤-endorphin and Met-enkephalin and the release of uroguanylin from these cells (Kokrashvili et al, 2009b). It is noteworthy that some enteroendocrine cells express signaling elements involved in taste transduction (the gut's luminal glucose sensor), initiating the incretin response to elicit the release of glucagon-like peptide 1 (Kokrashvili et al, 2009a).…”

Section: Transient Receptor Potential M4/m5 Subgroupmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family

Sweet

Clapham

2010

Pharmacological Reviews

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Release of Endogenous Opioids From Duodenal Enteroendocrine Cells Requires Trpm5

Cited by 77 publications

References 61 publications

Loss of high-frequency glucose-induced Ca ²⁺ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 ^−/− mice

Loss of high-frequency glucose-induced Ca ²⁺ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 ^−/− mice

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family

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Release of Endogenous Opioids From Duodenal Enteroendocrine Cells Requires Trpm5

Cited by 77 publications

References 61 publications

Loss of high-frequency glucose-induced Ca 2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 −/− mice

Loss of high-frequency glucose-induced Ca 2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 −/− mice

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family

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Loss of high-frequency glucose-induced Ca ²⁺ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 ^−/− mice

Loss of high-frequency glucose-induced Ca ²⁺ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5 ^−/− mice