Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes

Lewko, Barbara; Bryl, Ewa; Witkowski, Jacek M.; Latawiec, Elżbieta; Angielski, Stefan; Stępiński, Jan

doi:10.1093/ndt/gfh612

Cited by 20 publications

(18 citation statements)

References 15 publications

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“…Shear-stress-induced actin alignment in aortic endothelial cells in normoglycemic conditions was abolished in high-glucose media (30). Similarly, mechanical stress potentiated glucose uptake in podocytes and this effect was enhanced by high ambient glucose (34). While these studies provide information regarding the effect of mechanical strain on different cell types, the angiogenic responses of cardiac endothelial cells under diabetic conditions in conjunction with a mechanically strained microenvironment have yet to be elucidated.…”

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confidence: 99%

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Sheikh

Kuesel

Taghian

et al. 2014

American Journal of Physiology-Cell Physiology

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Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis, and endothelial dysfunction, with no treatment options currently available. Hyperglycemic memory by endothelial cells may play the key role in microvascular complications in diabetes, providing a potential target for therapeutic approaches. This study tested the hypothesis that a proangiogenic environment can augment diabetes-induced deficiencies in endothelial cell angiogenic and biomechanical responses. Endothelial responses were quantified for two models of diabetic conditions: 1) an in vitro acute and chronic hyperglycemia where normal cardiac endothelial cells were exposed to high-glucose media, and 2) an in vivo chronic diabetes model where the cells were isolated from rats with type I streptozotocin-induced diabetes. Capillary morphogenesis, VEGF and nitric oxide expression, cell morphology, orientation, proliferation, and apoptosis were determined for cells cultured on Matrigel or proangiogenic nanofiber hydrogel. The effects of biomechanical stimulation were assessed following cell exposure to uniaxial strain. The results demonstrate that diabetes alters cardiac endothelium angiogenic response, with differential effects of acute and chronic exposure to high-glucose conditions, consistent with the concept that endothelial cells may have a long-term “hyperglycemic memory” of the physiological environment in the body. Furthermore, endothelial cell exposure to strain significantly diminishes their angiogenic potential following strain application. Both diabetes and strain-associated deficiencies can be augmented in the proangiogenic nanofiber microenvironment. These findings may contribute to the development of novel approaches to reverse hyperglycemic memory of endothelium and enhance vascularization of the diabetic heart, where improved angiogenic and biomechanical responses can be the key factor to successful therapy.

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mentioning

confidence: 99%

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Sheikh

Kuesel

Taghian

et al. 2014

American Journal of Physiology-Cell Physiology

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“…Glomerulska hipertenzija uzrokuje glomerulsku hiperfiltraciju koja predstavlja osnavnu karakteristiku prve faze dijabetesne nefropatije (Tabela 2). Taj povećan glomerulski pritisak je mehanički stres koji deluje na ćelije glomerula i predstavlja jedan od dva najvažnija patogenetska faktora u nastanku dijabetesne nefropatije [10,14,15].…”

Section: Faktori Rizika I Patogeneza Dijabetesne Nefropatijeunclassified

“…Hiperglikemije, ali i glomerulska hipertenzija, uzrokuju povećan transport glukoze u ćeliju i ta povećana koncentracija glukoze u ćeli-jama vodi brojnim poremećajima. Glukoza, naime, nema direktan toksični efekat na ćelije glomerula nego njena povećana koncentracija menja produkciju različitih proteina i vodi nizu metaboličkih poremećaja koji uzrokuju leziju svih struktura glomerula [15]. Jedan od najvažnijih metaboličkih poremećaja je pre-komerna produkcija reaktivnih kiseoničkih radikala koji imaju brojna negativna biološka dejstva kao što su peroksidacija lipida ćelijskih membrana, oksidacija proteina, oštećenje DNK, vazokonstrikcija.…”

Section: Faktori Rizika I Patogeneza Dijabetesne Nefropatijeunclassified

“…Hiperglikemija uzrokuje i aktivaciju sistema renin-angiotenzin, pa kod bolesnika sa dijabetesom i pored normalne ili niske reninske aktivnosti plazme, intrarenalni angiotenzin može biti povišen usled njegove povećane produkcije u samom tkivu bubrega. Značaj povećane produkcije angiotenzina II nije samo u njegovom hemodinamskom dejstvu nego i brojnim drugim dejstvima [10,[15][16][17]. Hiperglikemija, glomerulska hipertenzija i poremećaji koje oni uzrokuje vode povećanoj aktivnost nuklearnog faktora κB [NFκB], ključnog faktora u regulaciji inflamacije.…”

Section: Faktori Rizika I Patogeneza Dijabetesne Nefropatijeunclassified

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Prevencija dijabetesne nefropatije

Djukanović

2012

Biomedicinska istraž.

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Kratak sadržajNeprekidni porast broja bolesnika sa dijabetesnom nefropatijom u terminalnoj insuficijenciji bubrega zahteva da se više pažnje posveti prevenciji ove bolesti. Savremene mere prevencije dijabetesne nefropatije zasnivaju se na poznavanju njene patogeneze. Dva glavna patogenetska faktora u nastanku dijabetesne nefropatije su hiperglikemija i povećan glomerulski pritisak. Glomerulska hipertenzija nastaje kao posledica smanjene rezistencije aferentne i nešto manje eferentne arteriole, što uzrokuju brojne vazoaktivne supstance koje se pojačano produkuju u dijabetesu. Ipak, glavni patogenetski faktor u nastanku dijabetesne nefropatije je hiperglikemija koja uslovljava povećan transport glukoze u ćelije glomerula. To vodi metaboličkim poremećajima u kojima se stvara niz produkata (reaktivni kiseonički radikali, krajnji produkt glikozilacije proteina, angiotenzin II) koji uzrokuju leziju svih struktura glomerula. Pored toga, ovi produkti stimulišu ćelije glomerula i tubula da pojačano produkuju citokine i faktore rasta koji dodatno oštećuju sve strukture nefrona i vode razvoju dijabetesne nefropatije.Kao najvažnije mere prevencije dijabetesne nefropatije smatraju se: (1) održa-vanje glikemije i HbA1C (<7,0%) blizu preporučenih vrednosti, (2) lečenje hipertenzije i održavanje krvnog pritiska ispod 130/80 mmHg, (3) blokada sistema renin-angiotenzin primenom inhibitora angiotenzin konvertujućeg enzima ili blokatora receptora angiotenzina, (4) prestanak pušenja, (5) izbegavanje nefrotoksičnih sredstava, (6) lečenje hiperlipidemije, (7) fizička aktivnost i (8) smanjenje telesne težine kod gojaznih. U budućnosti se očekuje da će novi lekovi, koji će uticati na dejstvo pojedinih faktora rasta, reaktivnih kiseoničkih radikala, produkata glikozilacije proteina, biti efikasna sredstva u prevenciji dijabetesne nefropatije. No do tada, dosledna i kontrolisana primena proverenih kasičnih preventivnih mera je obaveza svih zdravstvenih radnika koji se bave lečenjem bolesnika sa dijabetesom.

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“…With stretch, the membrane expression of the glucose transporter GLUT 2 is increased and expression of GLUT 4 decreased [41]. Mechanical stretch decreases podocyte proliferation and increases hypertrophy, these effects being mediated through the regulation of specific cell cycle regulatory proteins and activation of Erk1/2 and AKt [42,43].…”

Section: Stretchmentioning

confidence: 99%

The Podocyte: a Potential Therapeutic Target in Diabetic Nephropathy?

Marshall¹

2007

CPD

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Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways, loss of the alpha3beta1 integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumulation of abnormal extracellular matrix, apoptosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function. Some currently used therapies, such as tight glucose control and inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.

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Mechanical stress and glucose concentration modulate glucose transport in cultured rat podocytes

Cited by 20 publications

References 15 publications

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Prevencija dijabetesne nefropatije

The Podocyte: a Potential Therapeutic Target in Diabetic Nephropathy?

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