Non-muscle myosin IIA is involved in focal adhesion and actin remodelling controlling glucose-stimulated insulin secretion

Arous, Caroline; Rondas, Dieter; Halban, Philippe A.

doi:10.1007/s00125-012-2800-1

Cited by 38 publications

(48 citation statements)

References 46 publications

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“…A similar mechanism whereby FAK regulates the submembrane cAMP concentration may be present also in b-cells and FAK-inhibition was accordingly found to cause an increase in the basal cAMP concentration, possibly by release of phosphodiesterases from the dissolving focal adhesions. FAK has been shown to exert positive cues in glucosestimulated insulin secretion (Rondas et al 2011, Cai et al 2012, Arous et al 2013, but the present data indicate that FAK may serve an inhibitory role in this process as well. FAK inhibition reduced both first-and second-phase glucose-stimulated insulin secretion and reduced the number of docked granules (Rondas et al 2011(Rondas et al , 2012, indicating that the prevailing effect of FAK is to promote the exocytotic process.…”

Section: Discussioncontrasting

confidence: 59%

“…Cues from both extracellular matrix proteins and intracellular signaling events stimulate FAK activity, which in turn acts as a scaffold in focal adhesions and activates various downstream signaling pathways, such as AKT and ERK (Parsons 2003). In b-cells, FAK has been shown to convey signals from the extracellular matrix (Hammar et al 2004), promoting b-cell survival, and from glucose (Rondas et al 2011, Arous et al 2013, stimulating insulin secretion both in vitro and in vivo (Cai et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets

Alenkvist¹,

Dyachok²,

Tian³

et al. 2014

Journal of Endocrinology

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The Src homology-2 domain containing protein B (SHB) has previously been shown to function as a pleiotropic adapter protein, conveying signals from receptor tyrosine kinases to intracellular signaling intermediates. The overexpression of Shb in b-cells promotes b-cell proliferation by increased insulin receptor substrate (IRS) and focal adhesion kinase (FAK) activity, whereas Shb deficiency causes moderate glucose intolerance and impaired first-peak insulin secretion. Using an array of techniques, including live-cell imaging, patch-clamping, immunoblotting, and semi-quantitative PCR, we presently investigated the causes of the abnormal insulin secretory characteristics in Shb-knockout mice. Shb-knockout islets displayed an abnormal signaling signature with increased activities of FAK, IRS, and AKT. b-catenin protein expression was elevated and it showed increased nuclear localization. However, there were no major alterations in the gene expression of various proteins involved in the b-cell secretory machinery. Nor was Shb deficiency associated with changes in glucose-induced ATP generation or cytoplasmic Ca 2C handling. In contrast, the glucose-induced rise in cAMP, known to be important for the insulin secretory response, was delayed in the Shb-knockout compared with WT control. Inhibition of FAK increased the submembrane cAMP concentration, implicating FAK activity in the regulation of insulin exocytosis. In conclusion, Shb deficiency causes a chronic increase in b-cell FAK activity that perturbs the normal insulin secretory characteristics of b-cells, suggesting multi-faceted effects of FAK on insulin secretion depending on the mechanism of FAK activation.

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Section: Discussioncontrasting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets

Alenkvist¹,

Dyachok²,

Tian³

et al. 2014

Journal of Endocrinology

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“…The delayed cAMP response may be attributed to FAK-regulation of phosphodiesterase activity (Serrels et al 2010), which upon elevated FAK activity promotes the local breakdown of cAMP in the sub-membrane space (Alenkvist et al 2014). Both integrins and glucose promote increased b cell FAK activity with enhanced survival, proliferation and insulin secretion as a result (Rondas et al 2011, Cai et al 2012, Rondas et al 2012, Arous et al 2013. The data of the Shb knockout islets suggest negative effects of FAK as well, operating under conditions of chronic over-activity.…”

Section: Shb and B Cellsmentioning

confidence: 99%

The role of the Src Homology-2 domain containing protein B (SHB) in β cells

Welsh

Jamalpour

Zang

et al. 2015

Journal of Molecular Endocrinology

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This review will describe the SH2-domain signaling protein Src Homology-2 domain containing protein B (SHB) and its role in various physiological processes relating in particular to glucose homeostasis and b cell function. SHB operates downstream of several tyrosine kinase receptors and assembles signaling complexes in response to receptor activation by interacting with other signaling proteins via its other domains (proline-rich, phosphotyrosine-binding and tyrosine-phosphorylation sites). The subsequent responses are context-dependent. Absence of Shb in mice has been found to exert effects on hematopoiesis, angiogenesis and glucose metabolism. Specifically, first-phase insulin secretion in response to glucose was impaired and this effect was related to altered characteristics of focal adhesion kinase activation modulating signaling through Akt, ERK, b catenin and cAMP. It is believed that SHB plays a role in integrating adaptive responses to various stimuli by simultaneously modulating cellular responses in different cell-types, thus playing a role in maintaining physiological homeostasis.

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“…paxilin, talin, and vinculin and serving to route insulin granules toward the plasma membrane (24). This mechanism rests on focal adhesion kinase (FAK) whose activity regulates FA remodeling and turnover (25,26), and tension signaling (27), facilitating glucose-stimulated insulin secretion (28). This concept is consistent with biphasic insulin release because second phase transport of insulin granules requires F-actin as a motive force (29,30).…”

mentioning

confidence: 90%

CB1 Cannabinoid Receptors Couple to Focal Adhesion Kinase to Control Insulin Release

Malenczyk

Jazurek

Keimpema

et al. 2013

Journal of Biological Chemistry

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Background: Endocannabinoids can affect pancreatic ␤ cell physiology. Results: Anandamide and 2-arachidonoylglycerol binding to CB 1 receptors induces focal adhesion kinase phosphorylation, which is a prerequisite of insulin release. Conclusion: Focal adhesion kinase activation downstream from CB 1 receptors couples cytoskeletal reorganization to insulin release. Significance: Identifies the molecular blueprint of 2-arachidonoylglycerol signaling in the endocrine pancreas, and outlines a kinase activation cascade linking endocannabinoid signals to insulin release.

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Non-muscle myosin IIA is involved in focal adhesion and actin remodelling controlling glucose-stimulated insulin secretion

Cited by 38 publications

References 46 publications

Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets

Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets

The role of the Src Homology-2 domain containing protein B (SHB) in β cells

CB1 Cannabinoid Receptors Couple to Focal Adhesion Kinase to Control Insulin Release

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