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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of extracellular matrix on insulin production needs to be understood both to optimize the derivation of functional beta-cells for transplantation and to understand mechanisms controlling islet neogenesis and glucose homeostasis. In this study, we present evidence that adhesion to some common matrix constituents has a profound impact on the transcription, secretion, and storage of insulin by human beta-cells. The integrin-dependent adhesion of fetal beta-cells to both collagen IV and vitronectin induces significant glucose-independent insulin secretion and a substantial reciprocal decline in insulin content. Collagen IV, but not vitronectin, induces comparable responses in adult beta-cells. Inhibition of extracellular signal-regulated kinase activation abrogates matrix-induced insulin secretion and effectively preserves the insulin content of adherent beta-cells. Using real-time PCR, we demonstrate that adhesion of both fetal and adult beta-cells to collagen IV and vitronectin also results in the marked suppression of insulin gene transcription. Based on these findings, we contend that integrin-dependent adhesion and signaling in response to certain matrices can have a significant negative impact on insulin production by primary human beta-cells. Such responses were not found to be associated with cell death but may precede beta-cell dedifferentiation.
Diabetes 2006 Oct
PMID:Impact of defined matrix interactions on insulin production by cultured human beta-cells: effect on insulin content, secretion, and gene transcription. 1700 36

Studies of cell-matrix, cell-cell interaction or angiogenesis on different matrices require simultaneous comparison of read-out parameters from differently treated companion cells. The culture conditions (cell number, temperature and volume of culture medium) in different chambers are not completely equalized using conventional methods. It has been reported that cells growing in different environmental conditions may exhibit different proliferation patterns [P. Tracqui, J.W. Liu, O. Collin, J. Clement-Lacroix, E. Planus, Global analysis of endothelial cell line proliferation patterns based on nutrient-depletion models: implications for a standardization of cell proliferation assays, Cell Proliferat. 38(June (3)) (2005) 119-135]. Herein we describe an innovative chamber, which could resolve this problem by significantly improving the standardization of experimental conditions. The chamber was manufactured from a standard cell culture well by its division with a septum into two sections. We utilized the chamber and recently developed topological analysis to examine the effects of glycated matrices on the capillary-like network formation by endothelial cells. Glycated Collagen I resulted in dose-dependent changes to all measured topological characteristics of the capillary-like network, such as the number of branching points, number of meshes and total capillary length. These differences were observed only in neighbored compartments coated with different matrices, but not in the compartments coated with the same matrix. The novel chamber brings an opportunity for better standardization of experimental conditions and simultaneous observation of different experimental groups, reducing the possible effect of any systematic error.
Diabetes Res Clin Pract 2007 Jun
PMID:Glycated Collagen I (GC) impairs angiogenesis in vitro: a study using an innovative chamber for cell research. 1708 79

Glomerulosclerosis is one of the complications of diabetes that occurs after many years of uncontrolled hyperglycemia. Mesangial cells (MCs) exposed to high glucose (HG) for short periods have shown that transforming growth factor-beta (TGF-beta) and activated diacylglycerol-dependent protein kinase C (PKC) mediate increased collagen formation. Our study examined collagen formation by MCs exposed to HG for 8 weeks. Exposure to HG in overnight culture resulted in the activation of all PKC isoforms. In contrast, 8-week exposure to HG resulted in the persistent activation of PKC-delta, did not change PKC-alpha or -beta activity, and decreased PKC-epsilon activity while increasing collagen I and IV gene and protein expression. Collagen IV accumulation was reversed by specific PKC-delta inhibition. Collagen IV gene expression was completely normalized by TGF-beta neutralization; however, this was associated with plasminogen activator inhibitor-1 (PAI-1) overexpression and a modest reduction in collagen protein. Our studies suggest that prolonged exposure to HG results in PKC-delta-driven collagen accumulation by MCs mediated by PAI-1 but independent of TGF-beta.
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PMID:Effects of long-term elevated glucose on collagen formation by mesangial cells. 1772 2

We report the case of a 62-year-old man with a long-standing lesion on the dorsum of his right foot. The patient had diabetes mellitus and was under treatment with oral antidiabetic agents. The lesion contained abundant necrotic tissue, the borders showed evident signs of inflammation, and there was abundant prurulent exudate. Symptoms of infection were observed and a long course of broad-spectum antibiotics was administered. Given the site and characteristics of the lesion, unselective cleansing techniques were avoided. Collagen powder and silver dressing were applied to control bacteria and finally alginate and silicone sponge dressings were applied to soak up the exudate and keep the area moist. After 22 weeks of treatment, evident signs of improvement were observed, allowing the patient to perform activities of daily living.
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PMID:[Treatment of a long-standing lesion with early stimulation of wound healing]. 1803 41

The number of men with type II diabetes-associated erectile dysfunction (ED) continues to grow rapidly; however, the majority of basic science studies has examined mechanisms of ED in animal models of type I diabetes. In this study, we first establish an in vivo mouse model of type II diabetic ED using the leptin receptor mutated db/db and wild-type control BKS mouse. Furthermore, we hypothesized that dual mechanistic impairments contribute to the impaired erectile function in the type II diabetic mouse, altered vasoreactivity, and venoocclusive disorder. In vivo erectile function was measured as intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP) following electrical stimulation of the cavernosal nerve. Venoocclusion was assessed by the maintenance of elevated in vivo ICP following intracorporal saline infusion. Vasoreactivity of isolated cavernosum in response to contractile and dilatory stimulation was examined in vitro by myography. Collagen and elastin content were evaluated by quantification of hydroxyproline and desmosine, respectively, as well as by quantitative PCR and histological analysis of isolated cavernosum. Erectile function was significantly decreased in db/db vs. BKS mice in a manner consistent with impairments in venoocclusive ability and decreased inflow. Heightened vasoconstriction and attenuated dilation in cavernosum of db/db vs. BKS mice suggest an overall lowered relaxation ability and thus impaired filling of the cavernosal spaces. A decrease in desmosine and hydroxyproline as well as lowered mRNA levels for tropoelastin, fibrillin-1, and alpha1(I) collagen were detected. These vasoreactive and sinusoidal matrix alterations may alter tissue compliance dispensability, preventing the normal expansion necessary for erection.
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PMID:Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix. 1832 98

In the dermis, fibroblasts play an important role in the turnover of the dermal extracellular matrix. Collagen I and III, the most important dermal proteins of the extracellular matrix, are progressively altered during ageing and diabetes. For mimicking diabetic conditions, the cultured human dermal fibroblasts were incubated with increasing amounts of AGE-modified BSA and D-glucose for 24 hours. The expression of procollagen alpha2(I) and procollagen alpha1(III) mRNA was analyzed by quantitative real-time PCR. Our data revealed that the treatment of fibroblasts with AGE-modified BSA upregulated the expression of procollagen alpha2(I) and procollagen alpha1(III) mRNA in a dose-dependent manner. High glucose levels mildly induced a profibrogenic pattern, increasing the procollagen alpha2(I) mRNA expression whereas there was a downregulation tendency of procollagen alpha1(III) mRNA.
Exp Diabetes Res 2008
PMID:AGEs and glucose levels modulate type I and III procollagen mRNA synthesis in dermal fibroblasts cells culture. 1840 58

Collagen cross-links play important roles in the expression of bone strength and the proper biological function of bone. The cross-links of collagen can be roughly divided into two types : lysyl oxidase mediated cross-links (enzymatic immature and mature cross-links) and advanced glycation end-products (AGEs ; nonenzymatic cross-links, pentosidine) . Recently, we show that reduction in enzymatic cross-links and excessive formation of nonenzymatic crossl-links, pentosidine in bone could be important for explaining the variation of fracture susceptibility in osteoporosis (Osteoporos Int 17 (7) : 986-995, 2006) and diabetes (Osteoporos Int 17 (10) : 1514-1523, 2006) . We also demonstrate that urinary excretion AGEs cross-link, pentosidine is a novel risk for future vertebral fracture (J Bone Miner Metab 26 (1) : 93-100, 2008) . Such deteriorated cross-links in osteoporosis may be induced by moderately elevated homocysteine in sera (Osteoporos Int 2009 in press, Calcif Tissue Int 79 (3) : 160-168, 2006, J Bone Miner Metab 26 (6) : 595-602, 2008) . These results indicate that elevated serum or urine pentosidine and plasma homocysteine levels in osteoporosis and diabetes is useful marker for estimation of fracture risk independent of bone turnover and bone mineral density. In this review, I summarize the recent literatures regarding bone quality markers.
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PMID:[Biochemical markers of bone turnover. New aspect. Bone collagen metabolism: new biological markers for estimation of bone quality]. 1963 94

Collagen cross-linking, a major post-translational modification of collagen, plays important roles in the biological and biomechanical features of bone. Collagen cross-links can be divided into lysyl hydroxylase and lysyloxidase-mediated enzymatic immature divalent cross-links,mature trivalent pyridinoline and pyrrole cross-links, and glycation- or oxidation-induced non-enzymatic cross-links(advanced glycation end products) such as glucosepane and pentosidine. These types of cross-links differ in the mechanism of formation and in function. Material properties of newly synthesized collagen matrix may differ in tissue maturity and senescence from older matrix in terms of crosslink formation. Additionally, newly synthesized matrix in osteoporotic patients or diabetic patients may not necessarily be as well-made as age-matched healthy subjects. Data have accumulated that collagen cross-link formation affects not only the mineralization process but also microdamage formation. Consequently, collagen cross-linking is thought to affect the mechanical properties of bone. Furthermore,recent basic and clinical investigations of collagen cross-links seem to face a new era. For instance, serum or urine pentosidine levels are now being used to estimate future fracture risk in osteoporosis and diabetes. In this review, we describe age-related changes in collagen cross-links in bone and abnormalities of cross-links in osteoporosis and diabetes that have been reported in the literature.
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PMID:Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. 1976 59

Collagen-linked fluorescence at excitation/emission 370/440 nm has widely been used as a marker for advanced glycation in studies of aging, diabetic complications, and end-stage renal disease (ESRD). Diagnostic devices measuring skin autofluorescence at this wavelength revealed an association between fluorescence and cardiovascular morbidity and mortality. We now report the presence of a major fluorophore (LW-1) in human skin collagen which increases with age, diabetes, and ESRD. It has a molecular weight of 623.2Da, a UV maximum at 348 nm, and involves a lysine residue in an aromatic ring. LW-1 could not be synthesized using traditional glycation chemistry suggesting a complex mechanism of formation, perhaps related to hypoxia since elevated levels were also found in nondiabetic individuals with chronic lung disease.
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PMID:Partial characterization of the molecular nature of collagen-linked fluorescence: role of diabetes and end-stage renal disease. 1987 55

Microvascular network formation is required for the success of many therapies in regenerative medicine. The process of vessel assembly is fundamentally altered, however, in many people within the potential patient population, including the elderly and people with diabetes. Significant research has been performed to determine how cellular dysfunction contributes to this inadequate neovascularization, but alterations in the extracellular matrix (ECM) may also influence this process. Glycation of ECM proteins, specifically type I collagen, increases as people age and is accelerated due to uncontrolled diabetes. This glycation results in increased ECM stiffness and resistance to degradation. The goal of this research is to determine whether collagen glycation consistent with changes in aged (defined as people older than 80 years old) and diabetic individuals influences neovascularization. Collagen gels that were incubated in glucose-6-phopshate (G6P) for varying times exhibited cross-linking (26.2+/-8.1% and 31.3+/-5.6% for incubation in 375 mM G6P for 5 and 8 days, respectively), autofluorescence, and advanced glycation end product levels (666+/-481 and 2122+/-501 pmol/mg protein for 5 and 8 days of 375 mM G6P, respectively) consistent with aged and diabetic populations. Three-dimensional culture models showed that sprouting angiogenesis was delayed in collagen gels with high levels of glycation. When implanted in vivo, glycated gels were degraded (44.4+/-4.2% and 49.5+/-11.7% nondegraded gel remaining for gels incubated for 5 and 8 days in 375 mM G6P, respectively) and vascularized (75.5+/-32.0 and 73.7+/-23.6 vessels/mm(2)) more slowly than controls (22.3+/-9.9% gel remaining and 133.3+/-31.0 vessels/mm(2)). These results suggest that glycation of collagen can alter neovascularization and may contribute to alterations in vessel assembly observed as people age and due to diabetes.
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PMID:Collagen glycation alters neovascularization in vitro and in vivo. 2005 66


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