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  • American Diabetes Association  (2)
  • 1
    In: Diabetes, American Diabetes Association, Vol. 46, No. 5 ( 1997-05-01), p. 834-840
    Abstract: Accumulation of matrix proteins is a prominent feature of diabetic nephropathy. Glomerular visceral epithelial cells (GVECs) are important contributors to extracellular matrix (ECM) production in the glomerulus. Factors involved with increased accumulation of ECM proteins are high glucose, angiotensin II (ANG II), and transforming growth factor (TGF)-β. Therefore, we investigated the effects of high glucose and ANG II on fibronectin and TGF-β production by human GVECs in vitro. We found that ANG II had no effect on the production of fibronectin and TGF-β by GVECs. Using reverse transcriptase–polymerase chain reaction analysis, no ANG II receptor could be detected on these cells. However, high glucose induced a twofold increase in fibronectin (P & lt; 0.01) and a three- to sixfold increase in TGF-β (P & lt; 0.001) production. Similar results were obtained by analyzing the mRNA levels of fibronectin (increased 2.7-fold) and TGF-β (increased 3.5-fold). Addition of increasing concentrations of rTGF-β to control cells resulted in increased fibronectin production. Neutralizing antibodies against TGF-β significantly reversed the increase in fibronectin protein and mRNA caused by high glucose back to control levels. We conclude that high glucose concentrations stimulate the synthesis of fibronectin and that this effect is mediated by induction of TGF-β. These results suggest that in diabetic nephropathy, high glucose levels play a role in changing the matrix composition of the glomerular basement membrane through induction of TGF-β. Our results indicate that a contribution to this process by an effect of ANG II on GVECs seems unlikely.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1997
    detail.hit.zdb_id: 1501252-9
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 55, No. 2 ( 2006-02-01), p. 312-317
    Abstract: Islet transplantation is associated with a high rate of early graft failure caused by early immune attack and poor functionality of islets. Apoptosis of islet cells appears soon after islet isolation and primarily involves the β-cell. The purpose of this study was to determine the effect of ligation to extracellular matrix (ECM) proteins on survival of the islets of Langerhans following islet isolation. Islets that had been cultured for 24 h on collagen type I showed an islet survival of 59.7 ± 8.7%, while islets that had been cultured on collagen type IV and laminin showed an islet survival of 88.6 ± 10.3 and 94.3 ± 5.6%, respectively. Islets that had been pretreated with anti-β1 antibodies and argenin-glycin-aspartic acid (RGD) peptides showed a decrease in the level of apoptosis by a factor of 2.5 and 3.1, respectively, and an increase of phospho-Akt Ser 473 activity by a factor of 3.1 and 2.9, respectively, compared with untreated islets. When detached from their natural ECM surrounding in the pancreas, islet cells undergo apoptosis, unless islets are cultured on collagen IV or laminin or treated with anti-β1 integrin antibodies or RGD peptides to mimic ECM ligation. These results indicate that inhibition of anoikis may offer opportunities to improve function and viability of islet cells.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2006
    detail.hit.zdb_id: 1501252-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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