Role of PKCζ translocation in the development of type 2 diabetes in rats following continuous glucose infusion

Zhang, Jingfang; Yang, Jinhui; Wang, Guang-hao; Xia, Zhengyuan; Duan, Si‐Bo; Wu, Yong

doi:10.1002/dmrr.1056

Cited by 9 publications

(8 citation statements)

References 52 publications

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“…insulin-like growth factor-1 receptors and TrkB receptors) and other receptors involved in memory formation may regulate GluT4 [91][92][93][94] . Downstream of receptor activation, GluT4 translocation is regulated by several post-receptor signaling molecules critical for maintaining long term memory including insulin-like growth factor 2, brain-derived neurotrophic factor, Ca 2+ /calmodulindependent protein kinase II, phosphoinositide 3-kinase (PI3K), protein kinase A, MAPK, protein kinase-λ, and -protein kinase-ζ [91][92][93][94][95][96][97][98][99][100][101] . Some non-receptor activation-dependent conditions are associated with GluT4 trafficking and activity, such as cellular depolarization via elevated intracellular [Ca 2+ ] and elevated extracellular [K + ] 102-106 ; as noted below, this includes recruitment of GluT4 to the synapse as a consequence of neuronal activity 107 , a seminal recent finding that is consistent with prior work showing increased cerebellar GluT4 after prolonged exercise 108 .…”

Section: Mechanisms By Which Insulin Enhances Memorymentioning

confidence: 99%

“…CaMKII, DHA, PKC, PKA, BDNF, cellular depolarization, etc.) regulate GluT4 in adipocytes and muscle [91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106] . It will be important to determine which of these effects also occur in neurons.…”

Section: Peripheral Vs Central Regulation Of Glut4mentioning

confidence: 99%

“…T2DM and AD are linked mechanistically by insulin resistance: patients with AD have reduced brain insulin signalling 54,74,100 , accompanied by hypometabolism, and both insulin and insulin sensitizers have proven effective at ameliorating AD 60,74,212,213 . Conversely, T2DM is a major risk factor for AD, and leads to both elevated brain Aβ and impaired clearance of Aβ 54,74,[110][111][112][113][114][115][116][117] .…”

Section: Impaired Hippocampal Glut4 Translocation In Insulin Resistancementioning

confidence: 99%

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GluT4: A central player in hippocampal memory and brain insulin resistance

McNay

Pearson-Leary

2020

Experimental Neurology

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Insulin is now well-established as playing multiple roles within the brain, and specifically as regulating hippocampal cognitive processes and metabolism. Impairments to insulin signaling, such as those seen in type 2 diabetes and Alzheimer's disease, are associated with brain hypometabolism and cognitive impairment but the mechanisms of insulin's central effects are not determined. Several lines of research converge to suggest that the insulin -responsive glucose transporter GluT4 plays a central role in hippocampal memory processes, and that reduced activation of this transporter may underpin the cognitive impairments seen as a consequence of insulin resistance.

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Section: Mechanisms By Which Insulin Enhances Memorymentioning

confidence: 99%

Section: Peripheral Vs Central Regulation Of Glut4mentioning

confidence: 99%

Section: Impaired Hippocampal Glut4 Translocation In Insulin Resistancementioning

confidence: 99%

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GluT4: A central player in hippocampal memory and brain insulin resistance

McNay

Pearson-Leary

2020

Experimental Neurology

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“…Further understanding of the central role of caveolins in cardiac and insulin signaling under normal conditions will facilitate discovery of new treatment approaches for DCM. In insulin signaling cascades, phosphatidylinositol 3-kinase (PI3K) activates the major downstream effector Akt kinase, also termed protein kinase B (PKB), which modulates glucose uptake by facilitating GLUT4 translocation ( 136 ). Short-term exposure of mature adipocytes to glucose reduces Cav-1 expression and insulin sensitivity, but during adipocyte differentiation, chronic exposure to high glucose triggers adaptive response by adipocytes, manifested by increased protein expression of Cav-1, IR, and Akt ( 137 , 138 ).…”

Section: Caveolin and Its Potential As A Treatment Target For Diabeti...mentioning

confidence: 99%

The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy

Xia

Li²,

Wu³

et al. 2022

Front. Immunol.

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The diabetic population has been increasing in the past decades and diabetic cardiomyopathy (DCM), a pathology that is defined by the presence of cardiac remodeling and dysfunction without conventional cardiac risk factors such as hypertension and coronary heart diseases, would eventually lead to fatal heart failure in the absence of effective treatment. Impaired insulin signaling, commonly known as insulin resistance, plays an important role in the development of DCM. A family of integral membrane proteins named caveolins (mainly caveolin-1 and caveolin-3 in the myocardium) and a protein hormone adiponectin (APN) have all been shown to be important for maintaining normal insulin signaling. Abnormalities in caveolins and APN have respectively been demonstrated to cause DCM. This review aims to summarize recent research findings of the roles and mechanisms of caveolins and APN in the development of DCM, and also explore the possible interplay between caveolins and APN.

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“…One study found that PI3K subunit p85 transferred from cytosol to the cytomembrane within one minute under 10 −7 mol/L insulin stimulus in rat fibroblasts in which insulin receptor (IR) was highly expressed, while PKC ζ transferred from cytosol to the cytomembrane within one to 10 minutes [ 10 ], which suggested that PI3K activation occurred prior to PKC ζ, and PI3K may regulate PKC ζ directly in the cytomembrane. In a resting state, inactive PKC ζ locates in the cytoplasm, while it translocates to the cell membrane and becomes active upon stimulus [ 11 ]. However, how PKC ζ translocates from cytosol to the cytomembrane remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The Effect of SIN1 and Microtubules on Insulin Induced PKC ζ Activation

et al. 2017

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BackgroundProtein kinase C zeta (PKC ζ) plays an important role in insulin induced glycometabolism and insulin receptor (IR) associated signaling pathways. The full activation of PKC ζ depends on its translocation from cytosol to membrane and phosphorylation at Thr410. However, the mechanism of PKC ζ activation remains elusive. In this study, the effect of SIN1 and microtubules on insulin-induced PKC ζ activation was investigated.Material/MethodsHepG2 cells were stimulated with insulin for co-immunoprecipitation (co-IP) assay. The immunocomplex was captured by using anti-PKC ζ, anti-SIN1 or anti-FLAG antibodies and was subjected to western blotting analysis for detecting PKC ζ, SIN1, and β-tubulin protein expression level. The cells were intervened by small interfering RNA (siRNA) that targeted exon regions of SIN1. Then the glucose uptake ratio after cells were stimulated by insulin was measured. The PKC ζ insulin receptor levels in the membranes were analyzed. Cells stained with anti-PKC ζ, anti-SIN1 antibodies and probed with molecular probes were observed by immunofluorescence confocal microscopy.ResultsSIN1 interacted and co-located with PKC ζ by pleckstrin homology (PH) domain. Downregulation of SIN1 severely impaired PKC ζ translocation and phosphorylation induced by insulin. PKC ζ co-immunoprecipitated with β-tubulin at different intervals upon insulin stimulus, and the activation of PKC ζ was affected by paclitaxel and nocodazole.ConclusionsPKC ζ translocated from cytosol to membrane depending on SIN1, which suggested that PKC ζ may be activated directly by PI3K and the reaction probably carried out on microtubules in HepG2 cells.

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Role of PKCζ translocation in the development of type 2 diabetes in rats following continuous glucose infusion

Abstract: Translocation of PKCzeta may play a central role in the development of type 2 diabetes.

Cited by 9 publications

References 52 publications

GluT4: A central player in hippocampal memory and brain insulin resistance

GluT4: A central player in hippocampal memory and brain insulin resistance

The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy

The Effect of SIN1 and Microtubules on Insulin Induced PKC ζ Activation

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