Microtubules, microfilaments and insulin secretion

Howell, S. L.; Tyhurst, M.

doi:10.1007/bf00253571

Cited by 48 publications

(32 citation statements)

References 49 publications

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“…Early investigations into the mechanism of insulin release had revealed that the disruption of the MT network resulted in loss of insulin release, indicating that MT transport is essential for insulin secretion 25 . In contrast to MT effectors like nocodazole, treatment with colchicine abolished second phase insulin release but rendered the first phase intact [26][27][28][29] . We sought to confirm these findings and found a loss of second but not first phase insulin release for colchicine-treated MIN6m9 cells and isolated murine islets, whereas there was no insulin released in the case of treatment with nocodazole (data not shown).…”

Section: Disruption Of Basal Body Integrity Impairs Insulin Secretionmentioning

confidence: 84%

Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents

Christou-Savina²,

et al. 2014

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Type 2 diabetes mellitus is affecting more than 382 million people worldwide. Although much progress has been made, a comprehensive understanding of the underlying disease mechanism is still lacking. Here we report a role for the b-cell primary cilium in type 2 diabetes susceptibility. We find impaired glucose handling in young Bbs4 À / À mice before the onset of obesity. Basal body/ciliary perturbation in murine pancreatic islets leads to impaired first phase insulin release ex and in vivo. Insulin receptor is recruited to the cilium of stimulated b-cells and ciliary/basal body integrity is required for activation of downstream targets of insulin signalling. We also observe a reduction in the number of ciliated b-cells along with misregulated ciliary/basal body gene expression in pancreatic islets in a diabetic rat model. We suggest that ciliary function is implicated in insulin secretion and insulin signalling in the b-cell and that ciliary dysfunction could contribute to type 2 diabetes susceptibility.

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Section: Disruption Of Basal Body Integrity Impairs Insulin Secretionmentioning

confidence: 84%

Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents

Christou-Savina²,

et al. 2014

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“…In the case of prohormone convertase 2 (PCSK2), four spots were upregulated and three unchanged in islets exposed to elevated glucose compared with freshly isolated islets, which may reflect glucose-regulated post-translational modifications. In separate studies, actin, tubulin, related kinesins and probably also cytokeratins have been shown to be important for transport of insulin granules from the storage pool to the readily releasable pool [23][24][25]. The ATPase, H + transporting, lysosomal 70 M r , V1 subunit A, isoform 1 (ATP6V1A) causes intragranular acidification, which is a prerequisite for proinsulin cleavage by the endopeptidases [26], but also for granular release competence [27].…”

Section: Discussionmentioning

confidence: 99%

Glucose-induced changes of multiple mouse islet proteins analysed by two-dimensional gel electrophoresis and mass spectrometry

Ahmed

Bergsten

2005

Diabetologia

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Aims/hypothesis: The aim of this study was to investigate molecular mechanisms of glucose-induced changes in islets of Langerhans by analysing global changes in protein patterns of islets exposed to elevated glucose concentrations. Methods: Islets were isolated from C57BL/6J mice and used either directly or after exposure to 11 mmol/l glucose for 24 h. Islet protein profiles were obtained by twodimensional gel electrophoresis, and protein spots were identified by peptide mass fingerprinting using mass spectrometry. Results: Two-dimensional gels of freshly isolated islets and islets exposed to 11 mmol/l glucose contained 1,074 and 1,254 spots, respectively. The number of differentially expressed spots was 379, with 20 spots appearing as new proteins in islets exposed to 11 mmol/l glucose. We identified 124 spots corresponding to 77 protein entries and generated a reference map from freshly isolated islets. Actin, alpha enolase, cytokeratin 8, endoplasmin, glucoseregulated proteins, heat shock proteins, peroxiredoxins, prohormone convertase 2, protein disulphide isomerase, superoxide dismutase, tubulin, and V-type H + -ATPase (V1 subunit A) were upregulated in islets exposed to 11 mmol/l glucose. In contrast, exocrine proteins and secretagogin were downregulated in these islets compared with in freshly isolated islets. Conclusions/interpretation: The islet proteome approach revealed simultaneous changes in protein patterns of islets exposed to elevated glucose concentrations, indicating enhanced insulin synthesis, granular mobilisation and maturation, and increased stress response. The changes may be of relevance for the understanding of altered islet function in the hyperglycaemic state. It is expected that the islet reference map will become an important tool for dissecting multifactorial islet processes.

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“…Although constitutive vWf secretion is not affected, the microtubule-depolymerizing agents colchine and nocodazol were shown, in a previous study, to inhibit stimulated release of Weibel-Palade body contents and, in the present study, to nearly completely inhibit polarized release. Depolymerization of microtubules has also been shown to inhibit protein secretion in other systems (Antoine et al, 1980;Hail, 1984;Howell and Tyhurst, 1982;Redman et al, 1981). The situation that exists for membrane protein transport, however, appears to be different.…”

Section: Discussionmentioning

confidence: 99%

Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells.

Sporn

Marder

Wagner

1989

The Journal of Cell Biology

119

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Microtubules, microfilaments and insulin secretion

Cited by 48 publications

References 49 publications

Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents

Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents

Glucose-induced changes of multiple mouse islet proteins analysed by two-dimensional gel electrophoresis and mass spectrometry

Differing polarity of the constitutive and regulated secretory pathways for von Willebrand factor in endothelial cells.

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