Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside

Islam, Md. Shahidul

doi:10.1007/978-3-030-12457-1_37

Cited by 22 publications

(20 citation statements)

References 99 publications

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“…Because of the difficulty in obtaining pure human β-cells, it is common to use a variety of rodent insulinoma cells and glucagonoma cells for basic research in this field. The β-cells secrete insulin in response to stimulation by nutrients such as glucose, amino acids, and free fatty acids, neurotransmitters such as acetylcholine, and incretin hormones such as glucagon-like peptide-1 (GLP-1) [2]. The molecular mechanisms of stimulus-secretion coupling in the β-cells involve the intermediary metabolism of the nutrients in the cytoplasm and in the mitochondria, the participation of some G protein-coupled receptors (GPCR), and many ion channels [2].…”

Section: Introductionmentioning

confidence: 99%

“…The β-cells secrete insulin in response to stimulation by nutrients such as glucose, amino acids, and free fatty acids, neurotransmitters such as acetylcholine, and incretin hormones such as glucagon-like peptide-1 (GLP-1) [2]. The molecular mechanisms of stimulus-secretion coupling in the β-cells involve the intermediary metabolism of the nutrients in the cytoplasm and in the mitochondria, the participation of some G protein-coupled receptors (GPCR), and many ion channels [2]. Crucial events in the stimulus-secretion coupling are electrical activities, and increase in the concentration of Ca 2+ in the cytoplasm ([Ca 2+ ] i ), in the form of spikes, bursts, and oscillations [3].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Islam

2020

Cells

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Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Islam

2020

Cells

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“…To demonstrate the quantal nature of The above experiments demonstrate that β-cells show great variability in their Ca 2+ responses and a high level of spontaneous activity; supporting the notion of a β-cell's 'Ca 2+ fingerprint' (Prentki et al, 1988). As β-cells are frequently examined in artificially amplified resting and active states during experiments (Islam, 2010(Islam, , 2020, we have shown here that stimulation with the high glucose concentrations often employed, leading to high SERCA activity (Roe et al, 1994), obscures more subtle Ca 2+ changes taking place within the cell. It is probable that multiple stores and channels play a part in this process (Galione, 2019;Islam, 2020).…”

Section: While Over 96% Of Cells Exhibited a Clear Elevation Of Sub-mmentioning

confidence: 81%

“…As β-cells are frequently examined in artificially amplified resting and active states during experiments (Islam, 2010(Islam, , 2020, we have shown here that stimulation with the high glucose concentrations often employed, leading to high SERCA activity (Roe et al, 1994), obscures more subtle Ca 2+ changes taking place within the cell. It is probable that multiple stores and channels play a part in this process (Galione, 2019;Islam, 2020). The fact that the events occur after pre-incubation with thapsigargin, ruling out the ER as a source, are most striking when triggered with NAADP-AM which targets acidic stores, and are localised just beneath the membrane (the primary location of insulin granules, a subset of the acidic organelles in the β-cell (Orci, 1985)), is a strong suggestion that the source of these events are acidic Ca 2+ storage organelles.…”

Section: While Over 96% Of Cells Exhibited a Clear Elevation Of Sub-mmentioning

confidence: 81%

Glucose and NAADP trigger elementary intracellular β-cell Ca²⁺signals

Heister

Powell²,

Galione³

2020

Preprint

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Pancreatic β-cells release insulin upon a rise in blood glucose. The precise mechanisms of stimulus-secretion coupling, and its failure in Diabetes Mellitus Type 2, remain to be elucidated. The consensus model, as well as a class of currently prescribed anti-diabetic drugs, are based around the observation that glucose-evoked ATP production in β-cells leads to closure of cell membrane ATP-gated potassium (KATP) channels, plasma membrane depolarisation, Ca2+ influx, and finally the exocytosis of insulin granules (Ashcroft et al., 1984; Cook and Hales, 1984). However, it has been demonstrated by the inactivation of this pathway using genetic and pharmacological means that closure of the KATP channel alone may not be sufficient to explain all β-cell responses to glucose elevation (Henquin, 1998; Seghers et al., 2000). Here we show using total internal reflection fluorescence (TIRF) microscopy (Axelrod, 1981) that glucose as well as the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP), known to operate in β-cells (Johnson and Misler, 2002; Masgrau et al., 2003), lead to highly localised elementary intracellular Ca2+ signals. These were found to be obscured by measurements of global Ca2+ signals and the action of powerful SERCA-based sequestration mechanisms at the endoplasmic reticulum (ER). This is the first demonstration of elemental Ca2+ signals in response to NAADP, although they have been suspected (Davis et al., 2020). Optical quantal analysis of these events reveals a unitary event amplitude equivalent to that of known elementary Ca2+ signalling events, inositol trisphosphate (IP3) receptor mediated blips (Parker et al., 1996; Parker and Ivorra, 1990), and ryanodine receptor mediated sparks (Cheng et al., 1993). We propose that a mechanism based on these highly localised intracellular Ca2+ signalling events mediated by NAADP may initially operate in β-cells when they respond to elevations in blood glucose.

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“…The effect of cAMP on beta cell Ca 2+ signaling is not restricted to the voltage-dependent Ca2 + influx, but also involves a PKA-dependent and PKA-independent Ca 2+ mobilization from internal stores [97,[102][103][104]. Following beta cell depolarization and activation of VDCCs, Ca 2+ entering cytoplasm triggers additional release of Ca 2+ from intracellular compartments [105]. .…”

Section: The Effect Of Camp On [Ca 2+ ]Icmentioning

confidence: 99%

The Role of cAMP in Beta Cell Stimulus-Secretion and Inter-cellular Coupling

Stožer¹,

Leitgeb²,

Pohorec³

et al. 2021

Preprint

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Pancreatic beta cells secrete insulin in response to stimulation with glucose and other nutrients, and impaired insulin secretion plays a central role in development of diabetes mellitus. Pharmacological management of diabetes includes various antidiabetic drugs, including incretins. The incretin hormones, glucagon-like peptide-1 and gastric inhibitory polypeptide, potentiate glucose-stimulated insulin secretion by binding to G protein-coupled receptors, resulting in stimulation of adenylate cyclase and production of the secondary messenger cAMP, which exerts its intracellular effects through activation of protein kinase A or the guanine nucleotide exchange protein 2A. The mo-lecular mechanisms behind these two downstream signaling arms are still not fully elucidated and involve many steps in the stimulus-secretion coupling cascade, ranging from the proximal regula-tion of ion channel activity, to the central Ca2+ signal, and the most distal exocytosis. In addition to modifying intracellular coupling, the effect of cAMP on insulin secretion could also be at least partly explained by the impact on intercellular coupling. In this review, we systematically describe the possible roles of cAMP at these intra- and inter-cellular signaling nodes, keeping in mind the rele-vance for the whole organism and translation to humans.

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Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside

Cited by 22 publications

References 99 publications

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Glucose and NAADP trigger elementary intracellular β-cell Ca²⁺signals

The Role of cAMP in Beta Cell Stimulus-Secretion and Inter-cellular Coupling

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Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside

Cited by 22 publications

References 99 publications

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Glucose and NAADP trigger elementary intracellular β-cell Ca2+signals

The Role of cAMP in Beta Cell Stimulus-Secretion and Inter-cellular Coupling

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Glucose and NAADP trigger elementary intracellular β-cell Ca²⁺signals