Stromal Interaction Molecule 1 (STIM1) Regulates ATP-sensitive Potassium (KATP) and Store-operated Ca2+ Channels in MIN6 β-Cells

Leech, Colin A.; Kopp, Richard F.; Nelson, Heather A; Nandi, Jyotirmoy; Roe, Michael W.

doi:10.1074/jbc.m116.767681

Cited by 10 publications

(16 citation statements)

References 81 publications

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“…Thus, our data offer additional support to the notion that ER Ca 2+ stores shape the architecture of glucose-induced Ca 2+ oscillations as well as the β-cell insulin secretory response. Intriguingly, STIM1 was shown recently to interact with the sulfonylurea receptor 1 subunit of the K ATP channel and regulate β-cell K ATP activity in MIN6 cells (19). In this report, short hairpin RNA–mediated STIM1 knockdown reduced K ATP channel activation, whereas STIM1 reconstitution restored K ATP activity, suggesting that reductions in insulin secretion with STIM1 loss/SOCE inhibition may also result from impaired K ATP activity (19).…”

Section: Discussionmentioning

confidence: 99%

“…Mouse and human interleukin-1β (IL-1β), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were obtained from Invitrogen (Carlsbad, CA); and 2-aminoethoxydiphenyl borate (2-APB), 1-(5-chloronaphthalene-1-sulphonyl)- 1 H-hexahydro-1,4-diazepine (ML-9), and tunicamycin (TM) were obtained from Tocris Bioscience (Bristol, U.K.). Adenoviruses expressing STIM1 and Cre recombinase were from ViraQuest Inc. (North Liberty, IA) (19). Small interfering RNAs (siRNAs) were obtained from GE Healthcare (Lafayette, CO); and all other chemicals were from Sigma-Aldrich (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, defective SOCE has been associated with several clinical syndromes, including immunodeficiency, myopathy, Alzheimer disease, and vascular disease (14–18). Recently, pharmacologic inhibitors of SOCE or dominant-negative forms of either Orai1 or TRPC1 were shown to decrease insulin secretion in rat islets and clonal β-cell lines (11), while STIM1 was also shown to interact with the sulfonylurea receptor 1 subunit of the K ATP channel and regulate β-cell K ATP activity (19).…”

Section: Introductionmentioning

confidence: 99%

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Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell

et al. 2018

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Store-operated Ca entry (SOCE) is a dynamic process that leads to refilling of endoplasmic reticulum (ER) Ca stores through reversible gating of plasma membrane Ca channels by the ER Ca sensor Stromal Interaction Molecule 1 (STIM1). Pathogenic reductions in β-cell ER Ca have been observed in diabetes. However, a role for impaired SOCE in this phenotype has not been tested. We measured the expression of SOCE molecular components in human and rodent models of diabetes and found a specific reduction in STIM1 mRNA and protein levels in human islets from donors with type 2 diabetes (T2D), islets from hyperglycemic streptozotocin-treated mice, and INS-1 cells (rat insulinoma cells) treated with proinflammatory cytokines and palmitate. Pharmacologic SOCE inhibitors led to impaired islet Ca oscillations and insulin secretion, and these effects were phenocopied by β-cell STIM1 deletion. STIM1 deletion also led to reduced ER Ca storage and increased ER stress, whereas STIM1 gain of function rescued β-cell survival under proinflammatory conditions and improved insulin secretion in human islets from donors with T2D. Taken together, these data suggest that the loss of STIM1 and impaired SOCE contribute to ER Ca dyshomeostasis under diabetic conditions, whereas efforts to restore SOCE-mediated Ca transients may have the potential to improve β-cell health and function.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell

et al. 2018

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“…Phosphorylation strongly modulate Stim1/Orai1 interaction, required for the regulation of store operated Ca 2+ fluxes [44, 45]. A number of studies point to a role for SOCE in the control of Ca 2+ homeostasis/signaling during beta-cell activation mediated by nutrients [43, 46]. We provide additional evidence that the temporal control of phospho-regulation in the C-terminal tail of Stim1 is an important mechanism for the temporal control of SOCE during glucose-induced insulin secretion.…”

Section: Resultsmentioning

confidence: 99%

Glucose-dependent phosphorylation signaling pathways and crosstalk to mitochondrial respiration in insulin secreting cells

et al. 2019

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Background Glucose is the main secretagogue of pancreatic beta-cells. Uptake and metabolism of the nutrient stimulates the beta-cell to release the blood glucose lowering hormone insulin. This metabolic activation is associated with a pronounced increase in mitochondrial respiration. Glucose stimulation also initiates a number of signal transduction pathways for the coordinated regulation of multiple biological processes required for insulin secretion. Methods Shotgun proteomics including TiO 2 enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on lysates from glucose-stimulated INS-1E cells was used to identify glucose regulated phosphorylated proteins and signal transduction pathways. Kinase substrate enrichment analysis (KSEA) was applied to identify key regulated kinases and phosphatases. Glucose-induced oxygen consumption was measured using a XF96 Seahorse instrument to reveal cross talk between glucose-regulated kinases and mitochondrial activation. Results Our kinetic analysis of substrate phosphorylation reveal the molecular mechanism leading to rapid activation of insulin biogenesis, vesicle trafficking, insulin granule exocytosis and cytoskeleton remodeling. Kinase-substrate enrichment identified upstream kinases and phosphatases and time-dependent activity changes during glucose stimulation. Activity trajectories of well-known glucose-regulated kinases and phosphatases are described. In addition, we predict activity changes in a number of kinases including NUAK1, not or only poorly studied in the context of the pancreatic beta-cell. Furthermore, we pharmacologically tested whether signaling pathways predicted by kinase-substrate enrichment analysis affected glucose-dependent acceleration of mitochondrial respiration. We find that phosphoinositide 3-kinase, Ca2+/calmodulin dependent protein kinase and protein kinase C contribute to short-term regulation of energy metabolism. Conclusions Our results provide a global view into the regulation of kinases and phosphatases in insulin secreting cells and suggest cross talk between glucose-induced signal transduction and mitochondrial activation. Electronic supplementary material The online version of this article (10.1186/s12964-019-0326-6) contains supplementary material, which is available to authorized users.

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“…ATP-sensitive potassium channels (KATP), a functional heterooctameric complex, is one of the other crucial components of the β-cell membrane (Leech, Kopp, Nelson, Nandi, & Roe, 2017;N. Li et al, 2017).…”

Section: An Overview Of the Normal Physiology Of The β Cells And Inmentioning

confidence: 99%

Molecular aspects of pancreatic β‐cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA

Borujeni

Esfandiary

Baradaran

et al. 2018

Journal Cellular Physiology

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Metabolic syndrome is known as a frequent precursor of type 2 diabetes mellitus (T2D). This disease could affect 8% of the people worldwide. Given that pancreatic β‐cell dysfunction and loss have central roles in the initiation and progression of the disease, the understanding of cellular and molecular pathways associated with pancreatic β‐cell dysfunction can provide more information about the underlying pathways involved in T2D. Multiple lines evidence indicated that oxidative stress, microRNA, and long noncoding RNA play significant roles in various steps of diseases. Oxidative stress is one of the important factors involved in T2D pathogenesis. This could affect the function and survival of the β cell via activation or inhibition of several processes and targets, such as receptor‐signal transduction, enzyme activity, gene expression, ion channel transport, and apoptosis. Besides oxidative stress, microRNAs and noncoding RNAs have emerged as epigenetic regulators that could affect pancreatic β‐cell dysfunction. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in T2D pathogenesis. Here, we summarized the molecular aspects of pancreatic β‐cell dysfunction. Moreover, we highlighted the roles of oxidative stress, microRNAs, and noncoding RNAs in pancreatic β‐cell dysfunction.

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Stromal Interaction Molecule 1 (STIM1) Regulates ATP-sensitive Potassium (KATP) and Store-operated Ca2+ Channels in MIN6 β-Cells

Cited by 10 publications

References 81 publications

Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell

Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell

Glucose-dependent phosphorylation signaling pathways and crosstalk to mitochondrial respiration in insulin secreting cells

Molecular aspects of pancreatic β‐cell dysfunction: Oxidative stress, microRNA, and long noncoding RNA

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