A role of thyrotropin-releasing hormone in insulin secretion by isolated rat pancreatic islets

Najvirtova, Miroslava; Bačová, Zuzana; Mátéffyová, Adela; Štrbák, Vladimír

doi:10.1007/s00424-004-1362-6

Cited by 3 publications

(15 citation statements)

References 28 publications

(37 reference statements)

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“…Of particular interest is the fact that glucose has been found to activate Cl -currents in beta cells (ICl glucose ). Several lines of evidence indicate that the anion channels activated during regulatory volume decrease (RVD) after cell swelling (ICl swell regulatory volume decrease channels/ currents, RVDC) play a pivotal role in the process of insulin secretion: (i) osmotic cell swelling induces Cl -currents in insulin secreting cells (ICl swell ) [5][6][7][8]; (ii) glucose induces cell swelling in pancreatic beta cells [9]; (iii) glucose induces the activation of an anion conductance (ICl glucose ) with features resembling RVDC described in a great variety of cells [10][11][12][13][14][15][16]; (iv) cell swelling per se induces insulin release in clonal beta cells and isolated islets [9,[17][18][19][20][21]; (v) both ICl glucose and the swelling induced insulin release have been shown to be inhibited by the Cl -channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl)oxobutyric acid (DCPIB) and 4-hydroxytamoxifen [12,13,18,[22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Jakab

Grundbichler

Benický³

et al. 2006

Cell Physiol Biochem

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The metabolic coupling of insulin secretion by pancreatic beta cells is mediated by membrane depolarization due to increased glucose-driven ATP production and closure of K_ATP channels. Alternative pathways may involve the activation of anion channels by cell swelling upon glucose uptake. In INS-1E insulinoma cells superfusion with an isotonic solution containing 20 mM glucose or a 30% hypotonic solution leads to the activation of a chloride conductance with biophysical and pharmacological properties of anion currents activated in many other cell types during regulatory volume decrease (RVD), i.e. outward rectification, inactivation at positive membrane potentials and block by anion channel inhibitors like NPPB, DIDS, 4-hydroxytamoxifen and extracellular ATP. The current is not inhibited by tolbutamide and remains activated for at least 10 min when reducing the extracellular glucose concentration from 20 mM to 5 mM, but inactivates back to control levels when cells are exposed to a 20% hypertonic extracellular solution containing 20 mM glucose. This chloride current can likewise be induced by 20 mM 3-Omethylglucose, which is taken up but not metabolized by the cells, suggesting that cellular sugar uptake is involved in current activation. Fluorescence resonance energy transfer (FRET) experiments show that chloride current activation by 20 mM glucose and glucose-induced cell swelling are accompanied by a significant, transient redistribution of the membrane associated fraction of ICln, a multifunctional ‘connector hub’ protein involved in cell volume regulation and generation of RVD currents.

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Section: Introductionmentioning

confidence: 99%

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Jakab

Grundbichler

Benický³

et al. 2006

Cell Physiol Biochem

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“…Basal insulin secretion from islets of DS-treated rats is four times higher compared to controls (Fig. 2) and is decreased to control level after addition of 1nM TRH into medium [30].…”

Section: Effect Of Trh Absence and Administration On Insulin Secretionmentioning

confidence: 94%

“…TRH in physiological concentration (1 nM) does not affect basal (Fig. 2) insulin secretion from isolated intact rat pancreatic islets [30]. Basal insulin secretion from islets of DS-treated rats is four times higher compared to controls (Fig.…”

Section: Effect Of Trh Absence and Administration On Insulin Secretionmentioning

confidence: 96%

“…3A) insulin secretion from intact rat pancreatic islets is not affected by the presence of 1nM TRH [30]. The same dose of TRH has very dramatic effect on basal and glucose stimulated insulin release from TRH depleted islets (Fig.…”

Section: Effect Of Trh Absence and Administration On Insulin Secretionmentioning

confidence: 98%

“…DS acts as a selective inhibitor of peptidyl-glycine-α-amidating monooxygenase (PAM), the copper-, ascorbate-, and molecular oxygen-dependent enzyme catalyzing the last step of biosynthesis of α-amidated peptides, including TRH [28,29]. Five day pretreatment of adult rats by DS (200 mg/kg body weight subcutaneously daily) in our experiments decreased PAM activity in their pancreatic islets [30] to barely detectable level (6% of those achieved by vehicle treated ones). TRH in physiological concentration (1 nM) does not affect basal (Fig.…”

Section: Effect Of Trh Absence and Administration On Insulin Secretionmentioning

confidence: 99%

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Pancreatic Thyrotropin Releasing Hormone and Mechanism of Insulin Secretion

Štrbák¹

2018

Cell Physiol Biochem

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Thyrotropin releasing hormone (TRH; pGlu-His-ProNH2) is expressed also in pancreatic β cells where it is colocalized in secretory granules with insulin. High perinatal changes of the TRH gene expression and TRH concentrations in rat pancreatic islets coincide with the perinatal maturation of the adequate insulin secretory responsiveness to glucose and other nutrient secretagogues. TRH secretion from pancreatic islets is stimulated by glucose and inhibited by insulin. Disruption of the TRH gene in knockout mice results in hyperglycemia accompanied by impaired insulin secretory response to glucose. Progress in understanding TRH - insulin relations may be substantial for improving knowledge of pathophysiological mechanisms included in changes of insulin secretion with possible clinical impact. Block of the last step of biosynthesis of α-amidated peptides, including TRH by disulfiram (DS) treatment of adult male rats subcutaneously with 200 mg/kg for five days in our experiments resulted in barely detectable levels of peptidyl-glycine α-amidating monooxygenase (PAM) in their pancreatic islets. TRH in physiological concentration (1 nM) does not affect basal insulin secretion from intact rat pancreatic islets. In contrast, basal insulin secretion from islets of DS-treated rats is four times higher compared to controls and could not be further stimulated by high-glucose. The addition of 1 nM TRH into medium decreased immediately basal insulin secretion in DS (TRH lacking) islets to control level and normalized also their response to glucose. Interestingly, absence of the secretory response to glucose in islets from TRH depleted rats was connected with their increase of insulin content during stimulation. Glucose stimulation together with 1 nM TRH normalized also insulin content in DS islets. Apparently, high insulin content in islets from TRH depleted animals is a result of block of regulatory secretion pathway redirected to constitutional secretion which was corrected by the addition of TRH. Type 2 diabetes mellitus is a disease characterized by various range from predominant insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance. These symptoms suggest a possible role of TRH dysregulation. In conclusion, presence of TRH in β cells ensures appropriate low basal (constitutive) insulin secretion. Release of TRH induced by glucose and possibly by other secretagogues has autocrine effect resulting in directing insulin secretion to regulatory pathway reacting to stimulation. If some defects of insulin secretion could be treated by TRH, various ways of applications (also oral and nasal) could be utilized. Moreover, positive side effects shown in animal experiments may accompany the treatment: TRH has the potential to prevent apoptosis and promotes insulin-producing cell proliferation and has also aging-reversing properties.

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Bioactive peptides, networks and systems biology

Boonen

Creemers

Schoofs³

2009

BioEssays

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Bioactive peptides are a group of diverse intercellular signalling molecules. Almost half a century of research on this topic has resulted in an enormous amount of data. In this essay, a general perspective to interpret all these data will be given. In classical endocrinology, neuropeptides were thought of as simple signalling molecules that each elicit one response. However, the fact that the total bioactive peptide signal is far from simple puts this view under pressure. Cells and tissues express many different bioactive peptides and they are also able to respond to many different bioactive peptides, indicating that multiple receptors and signal transduction pathways are present in a single cell. Therefore, the authors suggest that the bioactive peptide signalling system should be regarded in the context of network and systems biology. Bioactive peptides can best be viewed as an extension of the protein interaction network that allows regulating and fine-tuning the metabolism of the different cells and tissues in the body. The cell thus responds to the 'peptidome' instead of to a single peptide. The intracellular part of this signalling network consists of the various signalling transduction cascades. Recently, new systems biology approaches have emerged for the modelling of cell signalling. The network and systems biology approach is also able to shed new light on the evolution of intercellular signalling.

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A role of thyrotropin-releasing hormone in insulin secretion by isolated rat pancreatic islets

Abstract: TRH plays an important role in the mechanism of insulin secretion and its response to glucose stimulation.

Cited by 3 publications

References 28 publications

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Pancreatic Thyrotropin Releasing Hormone and Mechanism of Insulin Secretion

Bioactive peptides, networks and systems biology

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