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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

To test the hypothesis that diabetes is a form of accelerated aging, the following observations were made. 1) The incidence rate of diabetes mellitus had its peak at around 50 years of age with a gradually decreasing rate thereafter. This was clearly different from the manner of incidence of such disease as arteriosclerosis which increased with advancing age. 2) 100g of the oral glucose tolerance test performed on elderly subjects aged 60 to 89 years revealed high incidence of abnormal tolerance, 21% diabetic and 53% borderline types. 3) The insulin secretory capacity to glucose load of subjects was not different from that of young and middle-aged subjects from 20 to 49 years old. Therefore, decreased tolerance to glucose load could not ba ascribed to deficient insulin secretion. 4) No abnormality of glucagon response to glucose load was found in the old. 5) Serum beta-N-acetylhexosaminidase activity was not increased in elderly subjects, again contrasting with the increased activity found in diabetics. 6) Both glycolytic and gluconeogenic enzyme activities were decreased in the liver of aged rats. 7) No specific abnromality in insulin secretory response was observed in Werner's syndrome which might be considered to be a model for aging. All the above observations do not support the aforementioned hypothesis. Abnormality of glucose tolerance frequently observed in elderly subjects appears to be caused by other pathogenesis than diabetes mellitus.
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PMID:[Aging and endocrine pancreas (author's transl)]. 34 Feb 93

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 replicative capacity of cultured human fibroblasts is discussed in relation to three areas, diabetes mellitus, expression of HL-A antigens, and interactions with polymerizing fibrin. The replicative capacity of cells is dimished in diabetes mellitus and certain related disorders such as progeria and Werner's syndrome, all of which feature accelerated aging. Expression of HL-A antigens is reduced in progeria fibroblasts compared to normal cultures at corresponding stages of passage. Normal cells show more subtle alteration during aging in vitro probably related to clonal heterogeneity and/or selection within mass cultures. Early-passage fibroblasts interact rapidly with polymerizing fibrin to form a mature clot which is then retracted by a process dependent on cellular integrity and active metabolism. Late-passage cultures are less active in both parameters as are fibroblasts from a subject with progeria. These observations, in total, may relate to altered self-recognition and certain autoimmune concomitants of aging in vivo. They may also help to explain impaired wound healing and increased predisposition to atherothrombosis in aging and diabetic individuals. This system of cultured human fibroblasts should serve as an excellent model to investigate the cellular and molecular basis of diabetes mellitus, aging and related pathology.
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PMID:Pathological implications of cell aging in vitro. 108 45

The clinical phenotype of Werner's syndrome (WS) includes short stature, premature cataracts, skin atrophy, osteoporosis, graying and loss of hair, neoplasia, diabetes mellitus, and arteriosclerosis. Cultured cells from patients with this autosomal recessive disorder exhibit chromosomal instability and a markedly reduced replicative lifespan and growth rate. To elucidate the cell cycle alterations associated with the growth deficit, we continuously labeled lymphoid cell lines from five WS patients and from four healthy adult controls with 5-bromodeoxyuridine. Bivariate Hoechst 33258/ethidium bromide flow cytometry revealed a 2.4-h prolongation in the minimal duration of the S phase of WS cells (P less than 0.005). Moreover, the fraction of proliferating cells irreversibly arrested in the S phase (5.4% vs 1.4% in controls) was significantly elevated in WS (P less than 0.001). Other cell cycle compartments were not significantly affected in WS cell lines. As a partial test of the hypothesis that the WS phenotype is due to a defect in DNA topoisomerase I (topo I) or DNA topoisomerase II (topo II) we exposed lymphoid cells from a healthy control to the topo I inhibitor camptothecin or to the topo II inhibitor 4'-(9-acridinylamino)methanesulfon-m-anisidine. The cell kinetic alterations elicited by these compounds differed from that exhibited by untreated WS patients. Thus, a primary defect in topo I or II is unlikely in WS. Our cell cycle results, however, provide important evidence that the biochemical genetic lesion is in fact expressed in lymphoblastoid cell lines, the most readily available cells from such subjects.
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PMID:Impaired S-phase transit of Werner syndrome cells expressed in lymphoblastoid cell lines. 132 51

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

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes.
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PMID:Diabetes secondary to genetic disorders. 144 74

Werner's syndrome is a genetic disease characterized by premature aging and is often associated with glucose intolerance due to insulin resistance. The clinical manifestations in this syndrome are preferentially expressed in the face and acral regions without apparent involvement of the trunk. We compared insulin receptor binding and amino acid uptake of fibroblasts derived from the forearm that had sclerodermoid features, and from the abdomen that was apparently normal in a patient with Werner's syndrome. In normal controls, specific insulin binding was not different in forearm and abdomen-derived fibroblasts (10.72 +/- 2.11%, 10.40 +/- 1.27%, respectively). In the patient, however, specific insulin binding was reduced in the fibroblasts derived from the forearm compared with those derived from the abdomen (3.55%, 8.16%, respectively). Scatchard analysis revealed that the reduction in insulin binding of the forearm fibroblasts from the patient was due to a reduction in receptor number with no change in receptor affinity. The dose-response curve for insulin of alpha-aminoisobutyric acid (AIB) uptake is shifted to the right in the fibroblasts derived from the acral area. The results show that in a patient with Werner's syndrome, regional differences occur in fibroblast insulin receptor binding and function. This suggests early phenotypic expression of the genetic abnormality of insulin receptor function in these patients.
Diabetes Res Clin Pract 1992 Feb
PMID:Regional differences in insulin receptor function in Werner's syndrome. 156 26

Werner's syndrome is a rare, autosomal recessive inherited disorder with a distinctive clinical picture. The characteristic physiognomy, shortness of stature with thin extremities, and large trophic ulcers are the key signs for the diagnosis. Premature greying of the hair and baldness, juvenile cataracts, a tendency to diabetes mellitus, hypogonadism, calcifications of the blood vessels, osteoporosis, metastatic calcifications of the soft tissue and an elevated incidence of neoplasms are further important features. We describe two patients with this disorder.
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PMID:[Werner syndrome with torpid trophic ulcera cruris]. 176 37


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