Decreased interaction of fibronectin, type IV collagen, and heparin due to nonenzymic glycation. Implications for diabetes mellitus

Tarsio, Joseph F.; Reger, Lorrel A.; Furcht, Leo T.

doi:10.1021/bi00378a006

Cited by 65 publications

(37 citation statements)

References 37 publications

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“…Consequences of advanced glycosylation product accumulation that may contribute to the development of diabetic retinal vasculopathy include impaired association of basement-membrane components such as heparan sulfate proteoglycan, laminin, and type IV collagen (26,27), stimulation of growth-promoting monokine production (28), and altered cell interactions with glucose-modified matrix (11). Although the relative contribution of each of these consequences of advanced glycosylation product accumulation remains to be determined, the overall inhibition of experimental diabetic retinopathy by aminoguanidine treatment suggests that an aminoguanidine-like compound may have therapeutic potential for the future prevention of human diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy.

Hammes

Martin

Federlin

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

470

266

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Retinal capillary closure induced by hyperglycemia is the principal pathophysiologic abnormality underlying diabetic retinopathy, but the mechaniss by which this induction occurs are not clear. Treatment of diabetic rats for 26 weeks with aminouanidine, an inhibitor of advanced glycosylation product formation, prevented a 2.6-fold accumulation of these products at branching sites of precapillary arterioles where abnormal periodic acid/Schiff reagentpositive deposits also occurred. A dine treatment completely prevented abnormal endothelial cell proliferation and signiflcantiy diminshed pericyte dropout. After 75 weeks, untreated diabetic animals developed an 18.6-fold increase in the number of acellular capillaries and formed capillary microaneurysms, characteristic pathologic features of background diabetic retinopathy. In contrast, aminoguanidinetreated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms. These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that a anqidine may have future therapeutic use in this disorder.Pathologic retinal changes are found in virtually 100%o of patients having type I diabetes for 15 yr or longer (1). Underlying the complex clinical manifestations of diabetic retinopathy are two fundamental abnormalities: increased retinal vascular permeability and progressive retinal vessel closure (2, 3). Digested retinal vasculature preparations from diabetic patients and animals characteristically show early pericyte loss which is followed by acellular capillary development and microaneurysm formation (4,5). The severity of these changes is associated with the degree of chronic hyperglycemia to which the diabetic retina has been exposed, but the mechanisms by which elevated glucose levels cause retinal damage are currently not known (6, 7). Potentially important mechanisms include increased polyol pathway activity, activation of protein kinase C by de novo diacylglycerol synthesis, and altered cell/matrix functions induced by accumulated advanced glycosylation end products (8-11).Recently the nucleophilic hydrazine compound aminoguanidine has been shown to inhibit the formation of advanced glycosylation products on collagen and basement membrane both in vitro and in vivo (12,13 pepsin/0.2% HCL. After 10 min in a water bath at room temperature, the retina was subjected to digestion by 3% trypsin/0.2 M Tris for 3.5 hr at 370C to remove the inner limiting membrane. The sample was then placed on a glass slide, and further digestion with trypsin was monitored under a dissecting microscope. The intact isolated retinal vessel preparation was washed with distilled H20 and air-dried. Retinal vessel preparations were stained with periodic acid/ Schiff reagent/hematoxylin (15) and photographed using a

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Section: Discussionmentioning

confidence: 99%

Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy.

Hammes

Martin

Federlin

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

470

266

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“…In order to test whether glycation of lAPP affects fibril solubility, 5-month-old fibrils were glycated in vitro. For this, fibrils were incubated in the presence of 0.5 M glucose for 15 days at +37°C, as described [11,12].…”

Section: Glycation and Solubility Of Lapp-fibrilsmentioning

confidence: 99%

Effects of beta cell granule components on human islet amyloid polypeptide fibril formation

et al. 1996

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Formation of amyloid-like fibrils in a solution of human islet amyloid polypeptide (hIAPP) with and without the presence of other IS-cell granule components was studied in vitro. Insulin at less than equimolar concentration strongly inhibited hIAPP fibrillogenesis. Proinsulin had a weaker inhibitory effect while C-peptide, Ca 2+ and Zn 2÷ each individually enhanced fibril formation. C-peptide combined with Ca 2+ had an inhibitory effect. Since IAPP was found almost exclusively in the halo fractions of isolated islet secretory granules, primarily the concentrations of C-peptide, Ca 2+ and possibly proinsulin may be crucial for the native state of IAPP. It is concluded that an imbalance between fibril formation enhancers and inhibitors may be of importance in the pathogenesis of amyloid in the islets of Langerhans.Key words: Fibril; Islet amyloid polypeptide; Non-insulindependent diabetes mellitus; In vitro; Granule loid properties in vitro while corresponding rat IAPP peptides do not [10]. This fibril formation of hIAPP occurs rapidly and spontaneously in aqueous solutions.With this knowledge, we hypothesized that there normally may exist a mechanism which hinders the formation of amyloid fibrils from IAPP in fl-cells and in the islets of Langerhans, the only sites where it is expressed at high concentrations. Since IAPP is stored together with insulin, proinsulin and C-peptide in the secretory granules, the influence of these three latter polypeptides on fibril formation was studied in vitro. Both calcium and zinc are present at high concentration in the fl-cell secretory granules and therefore the effect of these ions on fibril formation was included in the investigation. Finally, we determined the concentration of IAPP in the two fl-cell granule compartments. Materials and methods

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“…A fairly prolonged exposure to high concentrations of glucose may result in glycation and crosslinking of cell surface proteins and cause non-specific reduc-tion in receptor expression for a number of peptides [26]. However, in the present experiments where pericytes were exposed to 25 mmol/1 glucose for relatively short periods of time, there was no reduction in either the Kd or the number of binding sites for ET-1 compared to cells grown in 5 mmol/1 glucose: it was also the case for pericytes grown for up to 21 days in high glucose (unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Altered endothelin-1 induced contraction and second messenger generation in bovine retinal microvascular pericytes cultured in high glucose medium

et al. 1994

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SummaryThe effect of simulated hyperglycaemia on bovine retinal pericytes was studied following culture of these cells for 10 days under normal (5 mmol/1) and elevated (25 mmol/1) glucose conditions in the absence of endothelial cells. Pericytes cultured under high ambient glucose exhibited both a delayed and reduced contractile response following stimulation with endothelin-1. Stimulation with 10 7 mol/1 endothelin-1 for 30 s caused significant contraction in cells grown in both 5 mmol/1 and 25 mmol/1 glucose. The former also contracted significantly with 10 -8 mol/1 endothelin-1. Further, at all concentrations tested, statistical comparison of the time course of contraction showed a significant difference (p < 0.02) in the reduction of planimetric surface area between the two cell groups. Since neither binding of endothelin-1 nor the number of receptors for this peptide were significantly different (p > 0.1) between bovine retinal pericytes grown for 10 days under normo-or hyperglycaemic conditions, it became apparent that the altered contractility in bovine retinal pericytes following culture in high glucose must be due to post-binding intracellular disturbance(s). Indeed, both basal and 15 s post-stimulation with 10-8 mol/1 endothelin-1, levels of inositol trisphosphate were significantly reduced (p < 0.05 andp < 0.02, respectively) in pericytes cultured for 10days in 25 mmol/1 glucose. These results show that endothelialindependent alterations in contractility of pericytes occur when they are grown in conditions which simulate hyperglycaemia. The results also suggest that the observed attenuation in response to endothelin-1 stimulation evident in pericytes grown under simulated hyperglycaemic conditions is not due to alterations in peptide binding. [Diabetologia (1994) 37: 36-42] Key words Retinal microvascular pericytes, hyperglycaemia, endothelin-1, inositol (1,4,5) trisphosphate.The retinal microcirculation is devoid of extrinsic innervation and there is evidence that under normal conditions retinal blood flow may be regulated by changes in smooth muscle and pericyte tone mediated by endothelium-derived autacoids acting in paracrine fashion [1]. Recent work has shown that retinal capillary endothelial cells secrete endothelin-1 (ET-1), a potent vasoconstrictor, and that corresponding pericytes bear receptors to this peptide, suggesting the presence of a . ET-1 was first characterized and sequenced from the supernatant of cultured porcine aortic endothelial cells by Yanagisawa et al. [3]. It is the most potent vasoconstrictor known, causing contraction of vascular strips from humans and experimental animals in vitro [4], and is highly effective at the microcirculatory level [5]. We have previously demonstrated that ET-1 induces rapid increases in intracellular inositol (1,4,5) trisphosphate [Ins(1,4,5)P3] levels in cultured retinal pericytes and causes a sustained contraction response in these cells [6]. ET-1 also acts as a co-mitogen in pericytes in the presence of low levels of fetal calf serum [6]. ...

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Decreased interaction of fibronectin, type IV collagen, and heparin due to nonenzymic glycation. Implications for diabetes mellitus

Cited by 65 publications

References 37 publications

Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy.

Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy.

Effects of beta cell granule components on human islet amyloid polypeptide fibril formation

Altered endothelin-1 induced contraction and second messenger generation in bovine retinal microvascular pericytes cultured in high glucose medium

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