The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets

Leney, Sophie E; Tavaré, Jeremy M.

doi:10.1677/joe-09-0037

Cited by 134 publications

(93 citation statements)

References 186 publications

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“…Insulin is a peptide hormone secreted by the β-cells of the pancreatic islets of langerhans and maintains normal blood glucose levels by facilitating cellular glucose uptake, regulating carbohydrate, lipid and protein metabolism and promoting cell division and growth through its mitogenic effects [14] . The ability of insulin to stimulate glucose uptake into tissues is central to the maintenance of whole-body glucose homeostasis [15] . Type Ⅱ diabetes mellitus (T2DM), occurs when the production of insulin is not sufficient to overcome a difficulty the body has in properly using insulin.…”

Section: Resistancementioning

confidence: 99%

Hepatitis C virus infection and insulin resistance

Bose¹

2014

WJD

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Approximately 170 million people worldwide are chronically infected with hepatitis C virus (HCV). Chronic HCV infection is the leading cause for the development of liver fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and is the primary cause for liver transplantation in the western world. Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of type Ⅱ diabetes. Insulin resistance plays an important role in the development of various complications associated with HCV infection. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, HCC and resistance to anti-viral treatment. Thus, HCV associated insulin resistance is a therapeutic target at any stage of HCV infection. HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway. Various mechanisms have been proposed in regard to HCV mediated insulin resistance, involving up regulation of inflammatory cytokines, like tumor necrosis factor-α, phosphorylation of insulin-receptor substrate-1, Akt, up-regulation of gluconeogenic genes like glucose 6 phosphatase, phosphoenolpyruvate carboxykinase 2, and accumulation of lipid droplets. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Hepatitis C virus; Insulin resistance; Insulin receptor substrate 1; Protein kinase B; mammalian target of rapamycin/S6K1; Suppressor of cytokine signaling 3; Glucose transporter-4; Lipid metabolism; Antiviral therapy Core tip: Insulin resistance is one of the pathological features in patients with hepatitis C virus (HCV) infection and often leads to development of type Ⅱ diabetes. Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis, steatosis, hepatocellular carcinoma and resistance to anti-viral treatment. In this review, we summarize the available information on how HCV infection interferes with insulin signaling pathways.Bose SK, Ray R. Hepatitis C virus infection and insulin resistance. World J Diabetes 2014; 5(1): 52-58 Available from: URL:

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Section: Resistancementioning

confidence: 99%

Hepatitis C virus infection and insulin resistance

Bose¹

2014

WJD

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“…Insulin enhances the uptake of glucose into adipocytes and muscle cells by promoting the redistribution of the glucose transporter isoform 4 (GLUT4) from intracellular compartments to the cell surface (Huang and Czech, 2007;Larance et al, 2008;Leney and Tavaré, 2009). In basal adipocytes, the majority of GLUT4 is sequestered in tubulo-vesicular structures including recycling endosomes, the trans-Golgi Network (TGN), and in a discrete population of vesicles called GLUT4 storage vesicles (GSVs).…”

Section: Introductionmentioning

confidence: 99%

A role for Rab14 in the endocytic trafficking of GLUT4 in 3T3-L1 adipocytes

Reed

Hodgson²,

Song

et al. 2013

Journal of Cell Science

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SummaryInsulin enhances the uptake of glucose into adipocytes and muscle cells by promoting the redistribution of the glucose transporter isoform 4 (GLUT4) from intracellular compartments to the cell surface. Rab GTPases regulate the trafficking itinerary of GLUT4 and several have been found on immunopurified GLUT4 vesicles. Specifically, Rab14 has previously been implicated in GLUT4 trafficking in muscle although its role, if any, in adipocytes is poorly understood. Analysis of 3T3-L1 adipocytes using confocal microscopy demonstrated that endogenous GLUT4 and endogenous Rab14 exhibited a partial colocalisation. However, when wild-type Rab14 or a constitutively-active Rab14Q70L mutant were overexpressed in these cells, the colocalisation with both GLUT4 and IRAP became extensive. Interestingly, this colocalisation was restricted to enlarged 'ring-like' vesicular structures (mean diameter 1.3 mm), which were observed in the presence of overexpressed wild-type Rab14 and Rab14Q70L, but not an inactive Rab14S25N mutant. These enlarged vesicles contained markers of early endosomes and were rapidly filled by GLUT4 and transferrin undergoing endocytosis from the plasma membrane. The Rab14Q70L mutant reduced basal and insulin-stimulated cell surface GLUT4 levels, probably by retaining GLUT4 in an insulin-insensitive early endosomal compartment. Furthermore, shRNA-mediated depletion of Rab14 inhibited the transit of GLUT4 through early endosomal compartments towards vesicles and tubules in the perinuclear region. Given the previously reported role of Rab14 in trafficking between endosomes and the Golgi complex, we propose that the primary role of Rab14 in GLUT4 trafficking is to control the transit of internalised GLUT4 from early endosomes into the Golgi complex, rather than direct GLUT4 translocation to the plasma membrane.

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“…Glucose uptake by insulin stimulation occurs after the hormone binds to its specific membrane receptor called insulin receptor (IR) 16 . The IR is a heterotetrameric protein with intrinsic tyrosine kinase activity.…”

Section: Glucose Uptake Mediated By Insulin Hormonementioning

confidence: 99%

“…Successively, PDK-1 phosphorylates protein kinase B/Akt at serine/threonine kinase residue, which has a key role in insulin signaling pathway. When active, the Akt is responsible for the activation of AS160 (Akt substrate of 160 kDa) 16 . The AS160 can act in two significant ways on GLUT4 translocation to the periphery: 1) by reducing the "tethering" of the vesicle, by proteins called TUG, and thus releasing it to the periphery; 2) by increasing the activity of Rab proteins which will stimulate the translocation of these vesicles containing GLUT4 to the periphery.…”

Section: Glucose Uptake Mediated By Insulin Hormonementioning

confidence: 99%

“…Therefore, these activation mechanisms and the release of vesicles containing GLUT4 are essential for glucose homeostasis at baseline. The increase of GLUT4 and its translocation to the sarcoplasm are extremely important for performance and health 16 . Several studies have indicated that compromise at some point in this pathway can decrease glucose uptake, triggering important physiological changes that can lead to the development of various metabolic diseases, such as diabetes 17 .…”

Section: Glucose Uptake Mediated By Insulin Hormonementioning

confidence: 99%

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Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

Pereira

Moura

Muñoz

et al. 2017

Motriz: rev. educ. fis.

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-Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake. Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes. This transporter migrates to the plasma membrane and assists in glucose internalization. However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium act to regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulin levels. Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.

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The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets

Cited by 134 publications

References 186 publications

Hepatitis C virus infection and insulin resistance

Hepatitis C virus infection and insulin resistance

A role for Rab14 in the endocytic trafficking of GLUT4 in 3T3-L1 adipocytes

Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

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