Combined effect of insulin and high glucose concentration on albumin permeability in cultured rat podocytes

Piwkowska, Agnieszka; Rogacka, Dorota; Audzeyenka, Irena; Angielski, Stefan; Jankowski, Maciej

doi:10.1016/j.bbrc.2015.04.043

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…Recently, we showed that activation of the Nox4 subunit of NAD(P)H oxidase, through insulin induced changes in MYPT1 and MLC phosphorylation, activated PKGIα (Piwkowska et al, ). The same effect was observed in podocytes after a 5‐day incubation in HG (Piwkowska et al, ). Moreover, insulin disrupted the actin cytoskeleton in cultured rat podocytes (Piwkowska et al, ).…”

Section: The Role Of Pkgiα In Regulation Of the Constriction Apparatusupporting

confidence: 68%

“…The percentage of dimerized PKGIα increased by about 176% and 171% in the presence of insulin and HG, respectively. Importantly, the combined action of insulin and HG did not affect the maximal percentage of dimerized PKGIα (Piwkowska et al, ). Furthermore, insulin induced an increase in intracellular calcium concentration (Ca 2+ ) in podocytes.…”

Section: The Role Of Reactive Oxygen Species In the Regulation Of Pkgmentioning

confidence: 99%

“…Furthermore, one of the important findings was that insulin and HG had a synergistic effect on filtration barrier permeability to albumin. Both HG and insulin induced oxidation of PKGIα that was Nox4‐dependent, but their combined action did not influence the maximal percentage of dimerized PKGIα (Piwkowska et al, ). This suggested that the synergistic effect of these factors on podocyte albumin permeability was not dependent on oxidative activation of PKGIα.…”

Section: Role Of Pkgiα In the Regulation Of Filtration Barrier Permeamentioning

confidence: 99%

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Role of Protein Kinase G and Reactive Oxygen Species in the Regulation of Podocyte Function in Health and Disease

Piwkowska

2016

Journal Cellular Physiology

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Podocytes and their foot processes form an important cellular layer of the glomerular barrier involved in the regulation of glomerular permeability. Disturbing the function of podocytes plays a central role in the development of proteinuria in diabetic nephropathy. Retraction of the podocyte foot processes that form slit diaphragms is a common feature of proteinuria; although, the correlation between these events in not well understood. Notably, it is unclear whether podocyte foot processes are able to regulate slit diaphragm permeability and glomerular ultrafiltration. The occurrence of reactive oxygen species generation, insulin resistance, and hyperglycemia characterizes early stages of type 2 diabetes. Protein kinase G type I alpha (PKGIα) is an intracellular target for vasorelaxant factors. It is activated in both cGMP-dependent and cGMP-independent manners. Recently, we demonstrated a relationship between oxidative stress, PKGIα activation, actin reorganization, and changes in the permeability of the filtration barrier. This review discusses how redox imbalance affects both the activity of PKGIα and PKGI-dependent signaling pathways in podocytes. J. Cell. Physiol. 232: 691-697, 2017. © 2016 Wiley Periodicals, Inc.

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Section: The Role Of Pkgiα In Regulation Of the Constriction Apparatusupporting

confidence: 68%

Section: The Role Of Reactive Oxygen Species In the Regulation Of Pkgmentioning

confidence: 99%

Section: Role Of Pkgiα In the Regulation Of Filtration Barrier Permeamentioning

confidence: 99%

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Role of Protein Kinase G and Reactive Oxygen Species in the Regulation of Podocyte Function in Health and Disease

Piwkowska

2016

Journal Cellular Physiology

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“…Furthermore, increased albumin excretion has been observed in mice treated with the PTEN inhibitor [Lin et al., ]. AMPK and PTEN participate together in controlling insulin sensitivity in podocytes [Rogacka et al., ], in turn insulin signalling directs actin remodelling in order to glucose uptake [Piwkowska et al., ]. The current understanding of the AMPK as principal modulator of cytoskeleton organisation brings new opportunities and hopes in DN therapy.…”

Section: Impact Of Ampk On Podocyte Actin Cytoskeletonmentioning

confidence: 99%

AMPK signalling: Implications for podocyte biology in diabetic nephropathy

Szrejder

Piwkowska

2019

Biology of the Cell

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Diabetic nephropathy is a major long-term complication of diabetes mellitus and one of the most common causes of end-stage renal disease. Thickening of the glomerular basement membrane, glomerular cell hypertrophy and podocyte loss are among the main pathological changes that occur during diabetic nephropathy, resulting in proteinuria. Injury to podocytes, which are a crucial component of the glomerular filtration barrier, seems to play a key role in the development of diabetic nephropathy. Recent studies have suggested that dysregulation of AMPactivated kinase protein, which is an essential cellular energy sensor, may play a fundamental role in this process. The purpose of this review is to highlight the molecular mechanisms associated with AMP-activated protein kinase (AMPK) in podocytes that are involved in the pathogenesis of diabetic nephropathy.

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“…In vitro models have been developed to study podocyte permeability in response to drugs or high glucose, but do not account for the contribution of the GBM to permeability. [ 28–30 ] 3D and biomimetic podocyte cell culture models and glomerulus‐on‐a‐chip systems have also been developed to better recapitulate the in vivo microenvironment. [ 31–35 ] However, the physiological role of basement membranes is largely unaccounted for in most cell culture platforms.…”

Section: Introductionmentioning

confidence: 99%

A Biomimetic In Vitro Model of the Kidney Filtration Barrier Using Tissue‐Derived Glomerular Basement Membrane

Wang

Sant

Ferrell

2021

Adv Healthcare Materials

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The glomerular filtration barrier (GFB) filters the blood to remove toxins while retaining high molecular weight proteins in the circulation. The glomerular basement membrane (GBM) and podocytes, highly specialized epithelial cells, are critical components of the filtration barrier. The GBM serves as a physical barrier to passage of molecules into the filtrate. Podocytes adhere to the filtrate side of the GBM and further restrict passage of high molecular weight molecules into the filtrate. Here, a 3D cell culture model of the glomerular filtration barrier to evaluate the role of the GBM and podocytes in mediating molecular diffusion is developed. GBM is isolated from mammalian kidneys to recapitulate the composition and mechanics of the in vivo basement membrane. The GFB model exhibits molecular selectivity that is comparable to the in vivo filtration barrier. The GBM alone provides a stringent barrier to passage of albumin and Ficoll. Podocytes further restrict molecular diffusion. Damage to the GBM that is typical of diabetic kidney disease is simulated using hypochlorous acid and results in increased molecular diffusion. This system can serve as a platform to evaluate the effects of GBM damage, podocyte injury, and reciprocal effects of altered podocyte–GBM interactions on kidney microvascular permeability.

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Combined effect of insulin and high glucose concentration on albumin permeability in cultured rat podocytes

Cited by 10 publications

References 23 publications

Role of Protein Kinase G and Reactive Oxygen Species in the Regulation of Podocyte Function in Health and Disease

Role of Protein Kinase G and Reactive Oxygen Species in the Regulation of Podocyte Function in Health and Disease

AMPK signalling: Implications for podocyte biology in diabetic nephropathy

A Biomimetic In Vitro Model of the Kidney Filtration Barrier Using Tissue‐Derived Glomerular Basement Membrane

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