Actin Dynamics Regulated by the Balance of Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) and Cofilin Activities Determines the Biphasic Response of Glucose-induced Insulin Secretion

Uenishi, Eita; Shibasaki, Tadao; Takahashi, Harumi; Seki, Chihiro; Hamaguchi, Hitomi; Yasuda, Takahiro; Tatebe, Masato; Oiso, Yutaka; Takenawa, Tadaomi; Seino, Susumu

doi:10.1074/jbc.m113.464420

Cited by 45 publications

(42 citation statements)

References 61 publications

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“…Both a negative role as a physical fusion barrier and a positive role of promoting vesicle transport and exocytosis have been proposed (86,87). In insulin-secreting cells, a fairly selective role of actin remodeling in the second phase of GSIS has been reported (11,13,14,16,61). Similarly, we observed a selective decrease in the second phase of GSIS along with strong actin reorganization in Dnm2 KO β cells.…”

Section: Discussionsupporting

confidence: 65%

“…Moreover, increasing evidence supports an emerging model in which the actin cytoskeleton plays a critical role in biphasic GSIS (10,11) through granule mobilization and recruitment from the reserve pool to the PM. Many actin remodeling molecules, such as the Rho GTPase family proteins Cdc42 (13) and RAC1 (14), PAK1 (15), N-WASP (16), and PPARβ/δ (17), selectively regulate the second phase of GSIS, and perturbations of microtubules (18) and kinesin-1 (19) disrupt the second phase.…”

Section: Introductionmentioning

confidence: 99%

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Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Fan¹,

Chen²,

Wu³

et al. 2015

Journal of Clinical Investigation

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Fan¹,

Chen²,

Wu³

et al. 2015

Journal of Clinical Investigation

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“…acute smooth muscle contractility following Rho activation (55,56). In accordance with our observation in smooth muscle, F-actin remodeling has been reported to be involved in glucoseinduced insulin secretion in pancreatic ␤-cells, partly via inhibition of cofilin (57). Concurring with an increased Rho activation and actin polymerization, we found that glucose promotes the expression of contractile smooth muscle markers at both mRNA and protein levels.…”

Section: Table 2 Clinical Characteristics Of Left Internal Mammary Arsupporting

confidence: 75%

Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization

Hien¹,

Turczyńska²,

Dahan³

et al. 2016

Journal of Biological Chemistry

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Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells, but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hypercontractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, quantitative PCR, and Western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers were increased in isolated smooth muscle cells cultured under high compared with low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization, and myocardin-related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.Diabetes confers a 2-4-fold excess risk for a wide range of cardiovascular diseases, including macrovascular complications leading to coronary heart disease and ischemic stroke, as well as microvascular diseases, such as nephropathy and retinopathy (1, 2). Based on current trends, the rising incidence of diabetes (expected to reach 333 million people worldwide by 2025) will undoubtedly equate to increased cardiovascular mortality. Chronic hyperglycemia has long been recognized as an independent risk factor for cardiovascular disease (3, 4). Importantly, the progressive relationship between glucose levels and cardiovascular risk extends below the threshold for diabetes diagnosis (fasting plasma glucose Ն7.0 mmol/liter or 2-h plasma glucose Ն11.1 mmol/liter (2, 3)), and more recently, even transient hyper-and hypoglycemia have emerged as important determinants of cardiovascular disease (5). Despite the vast clinical and epidemiological experience linking blood glucose and poor glucose control to the development and progression of cardiovascular disease, the underlying molecular mechanisms leading to vascular dysfunction and disease are poorly understood (6).It has been well established that hyperglycemia results in vascular hyperreactivity in diabetic patients (7) and animal models (8 -10). Part of this effect may be attributed to a decrease in nitric oxide (NO) bioavailability as well as a reduced respon...

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“…7 A and C). A higher density of microtubules upon taxol treatment could also increase the probability of SGs to switch direction, thereby decreasing their D. Glucose stimulation, which induces FA remodeling (52,53), recruited SGs to the highly dynamic component (Fig. 2C).…”

Section: Discussionmentioning

confidence: 99%

Aged insulin granules display reduced microtubule-dependent mobility and are disposed within actin-positive multigranular bodies

Hoboth

Müller

Ivanova

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Insulin secretion is key for glucose homeostasis. Insulin secretory granules (SGs) exist in different functional pools, with young SGs being more mobile and preferentially secreted. However, the principles governing the mobility of age-distinct SGs remain undefined. Using the time-reporter insulin-SNAP to track age-distinct SGs we now show that their dynamics can be classified into three components: highly dynamic, restricted, and nearly immobile. Young SGs display all three components, whereas old SGs are either restricted or nearly immobile. Both glucose stimulation and F-actin depolymerization recruit a fraction of nearly immobile young, but not old, SGs for highly dynamic, microtubule-dependent transport. Moreover, F-actin marks multigranular bodies/lysosomes containing aged SGs. These data demonstrate that SGs lose their responsiveness to glucose stimulation and competence for microtubule-mediated transport over time while changing their relationship with F-actin.

show abstract

Actin Dynamics Regulated by the Balance of Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) and Cofilin Activities Determines the Biphasic Response of Glucose-induced Insulin Secretion

Cited by 45 publications

References 61 publications

Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

Elevated Glucose Levels Promote Contractile and Cytoskeletal Gene Expression in Vascular Smooth Muscle via Rho/Protein Kinase C and Actin Polymerization

Aged insulin granules display reduced microtubule-dependent mobility and are disposed within actin-positive multigranular bodies

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