Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of Werner syndrome is reported. The patient was prematurely old, had skin atrophy, characteristic posterior subcapsular cataracts and prepubertal primary hypogonadism. Additional ocular features compatible with premature ageing included presbyopia, arcus seniles and diminished tear flow. Diabetes mellitus, poliosis, baldness and beak-like nose were not present.
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PMID:Werner syndrome. 26 94

We have carried out studies on cultured human fibroblasts in an attempt to trace the origins of age-dependent disorders to the cellular and molecular levels. Three interrelated areas are discussed. First, skin donors with diabetes mellitus (a disease complex that features inappropriate hyperglycemia) produce cultured fibroblasts with a moderate reduction in growth capacity, while two inherited disorders of inappropriate hyperglycemia and premature aging, progeria and Werner syndrome, yield fibroblast cultures with more severely impaired growth capacity. Second, there is a decreased response of progeria level and donor age; evidence is presented that this defective hormone responsiveness in aging cells may reside at the hormone receptor on the surface membrane, the cyclic AMP system, the intracellular enzymatic machinery, or all of these sites. Third, tissue factor, a procoagulant that activates the extrinsic clotting mechanism, is more abundant in cells from the premature aging syndromes of progeria and Werner syndrome. Fibroblast aging in vitro may help to explain various concomitants of normal aging and diabetes mellitus including cell dropout, impairment of hormone responsiveness, and increased atherothrombosis.
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PMID:In vitro studies of age-associated diseases. 42 66

In order to trace the origins of age-dependent diseases to the cellular level, we studied cultured human fibroblasts from subjects with 3 discrete inherited disorders and normal controls of various ages. Skin fibroblasts from subjects with progeria and Werner syndrome had a moderate to severe reduction in growth capacity, whereas cells from subjects with diabetes mellitus had a more subtle growth impairment. There was a decreased response of progeric fibroblasts to insulin-like hormones, and in normal cells the response decreased as a function of the passage level and donor age. Tissue factor, a procoagulant, was more abundant in progeric and Werner fibroblasts. An understanding of fibroblast aging in vitro may help us explain various concomitant phenomena of organismic aging such as diabetes mellitus, cell dropout, impaired hormone responsiveness, and increased atherothrombosis.
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PMID:Studies on age-related diseases in cultured skin fibroblasts. 44 74

The effect of insulin on the transport of proline has been studied in cultured fibroblasts from normal individuals, non-insulin-dependent diabetic patients, and patients with Werner syndrome. In fibroblasts from normal individuals and those with diabetes mellitus, incubation with 10(-7) M insulin resulted in more than a twofold increase in the transport rate after about 14 h incubation. In contrast, fibroblasts from patients with Werner syndrome had a markedly attenuated response to insulin, suggesting a defect in insulin action on the transport of this amino acid in Werner syndrome.
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PMID:Effect of insulin on the proline transport activity in cultured fibroblasts from patients with Werner syndrome. 141 49

It could be demonstrated that plasma and tissue fibronectin (FN) increase with age. Some age dependent diseases as diabetes, osteoarthritis and Werner syndrome produce also an increase of tissue fibronectin biosynthesis. Plasma fibronectin decreases in diabetes and in breast cancer. Alternative splicing of the FN gene appears also to vary with age and in some related pathologies. Nutritional status and UV light also influence FN biosynthesis. It appears therefore that the determination of plasma FN and its isoforms as well as the study of tissue FN may be of interest for the study of chronological aging and related pathologies.
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PMID:[Fibronectin, aging and related pathologies]. 183 21

We describe a new familial syndrome in three siblings; it is biochemically characterized by a combined defect of the action of the three related peptides insulin, insulin-like growth factor I (IGF I) and epidermal growth factor (EGF). Clinically, the disease has features of Werner syndrome with lipodystrophy, scleroderma-like alterations of the skin, alterations of the skeleton and contractures of joints. In addition, one of the patients has an insulin-resistant diabetes mellitus. Studies with cultured fibroblasts obtained from skin biopsies show a markedly reduced stimulation of RNA synthesis by the three growth factors and a decreased insulin stimulation of 2-deoxy-D-glucose uptake as compared with normal controls. Receptor binding of the three peptides occurred with normal capacity and affinity. We conclude that the signal transfer of different growth factors has a common denominator at the postreceptor level.
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PMID:A new familial syndrome with impaired function of three related peptide growth factors. 247 23

Recent concepts on the mechanisms of aging of extracellular matrix (EM) are reviewed as well as its involvement in age-associated diseases. Cell differentiation, histogenesis and organogenesis can be analyzed in terms of the program of the biosynthesis of EM macromolecules during development, maturation and aging. The most important biological role of EM is the integration of cells in tissues, of tissues in organs and of organs in the whole organism. EM can directly influence cell behavior through the contact between EM and the genome mediated by structural glycoproteins (fibronectin, laminin, elastonectin, etc.) interacting with other EM macromolecules (collagen, proteoglycans, elastin) and the cytoskeleton by trans-membrane receptors (integrins). Most age-associated diseases exhibit a deviation (qualitative or quantitative) from the normal program of EM biosynthesis. Three examples are analyzed in some detail: atherosclerosis, diabetes and malignant tumors. The degradation of elastic fibers catalyzed by cellular elastase-type enzymes is observed in atherosclerosis and also in emphysema and skin aging. Several of these enzymes were isolated and characterized from platelets, fibroblasts, smooth muscle cells and lipoproteins. The biosynthesis of some of them increases with age and facilitates cell migration. Plasma fibronectin increases with age exponentially. This increase is absent or strongly attenuated in diabetes and some cancers. Tissue fibronectin increases in diabetes, Werner syndrome and in the peritumoral desmoplastic reaction while most tumor cells can no more retain fibronectin on their membrane facilitating their movement in the organism. These examples demonstrate the importance of the study of cell matrix interactions for gerontology.
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PMID:Aging of the extracellular matrix and its pathology. 328 58

The Werner syndrome (WS) is characterized by the premature onset and accelerated rate of development of major geriatric disorders, including atherosclerosis, diabetes mellitus, osteoporosis, ocular cataracts, and various neoplasms. Cultures of WS skin-fibroblastlike cells have been previously shown to undergo accelerated rates of decline of the replicative potentials and to exhibit variegated chromosomal translocations and deletions. Since the replicative decline of normal somatic cells is associated with a loss of telomeric repeats, we investigated the kinetics of telomeric repeat loss in WS cells. The mean length of telomere restriction fragments (TRF) from the earliest passages of WS cells studied was not shorter than those of controls, possibly reflecting selective pressure for subsets of cells with relatively high residual replicative capacity. Statistical evidence indicated an accelerated shortening of TRF length in serially passaged WS cultures, but the mean TRF lengths of WS cultures that had ceased replicating were significantly longer than those of senescent controls. Thus, while accelerated loss of telomeric repeats could potentially explain the rapid decline in proliferation of WS cells, it is possible that WS cells exit the cell cycle via mechanisms that differ from those of replicatively senescent cells from control subjects.
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PMID:Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells. 864 91

The Werner syndrome (WS) is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus (NIDDM), ocular cataracts and osteoporosis [Epstein et al., 1966]. The major cause of death (at a median age of 47) is myocardial infarction (MI) [Epstein et al., 1966]. The WS mutation involves a member (WRN) of the RecQ family of helicases and may perturb DNA replication, repair, recombination, transcription, or chromosomal segregation [Yu et al., 1996]. We now report data on 149 MI cases and age-matched controls suggesting that a polymorphic WRN variant is associated with increased risk for MI. Based on our data, homozygosity for a cysteine at amino acid 1367 (the most prevalent genotype) predicts a 2.78 times greater risk of MI (95% confidence intervals: 1.23 to 6.86). The variant was not significantly associated with NIDDM. The two alleles (cysteine vs. arginine) could influence helicase activity, turnover, macromolecular interactions or, alternatively, could be markers for haplotypes influencing WRN regulation or reflecting gene action at linked loci. However, given the caveats implicit in genetic association studies, it is imperative that the present results be replicated in independent populations.
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PMID:Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population. 902 Oct 29

Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involved in the mechanism of atherosclerosis in this syndrome. Previously we revealed that the plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that the PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The results show a high concentration of plasma PAI-1. One of the well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentrations of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentrations of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome.
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PMID:Increased blood plasminogen activator inhibitor-1 and intercellular adhesion molecule-1 as possible risk factors of atherosclerosis in Werner syndrome. 918 38


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