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 patient with Werner's syndrome, partial lipoatrophy and diabetes mellitus presented several of the metabolic alterations found in obesity and maturity-onset diabetes, in spite of a total body-fat mass which was markedly reduced when compared to randomly-selected women. The data show elevated blood sugar and free fatty acids, hyperinsulinemia, elevated glucaon and suppressed growth-hormone levels. Metabolic studies with isolated adipocytes show evidence of increased lipolytic response to catecholamines, diminished binding of insulin and decreased antilipolytic effect of this hormone. A striking feature of this patient's adipose tissue was the contrast between lipoatrophy in the subcutaneous tissue of the extremities and augmented abdominatl subcutaneous adipose tissue. The adipocyte size in this region was very large (1.6 micrograms lipid/cell) and among the largest ever recorded in this laboratory. It is proposed that a 'regional adiposity', particularly in the abdominal area, with enhanced adipocyte size and adipocyte metabolic contributions, may promote the metabolic events and alterations that are more typically observed in the generalized form of obesity.
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PMID:Possible systemic metabolic effects of regional adiposity in a patient with Werner's syndrome. 699 62

A typical patient with this uncommon premature aging syndrome was followed over a period of four and a half years until his death. He presented the characteristic clinical features, as well as the complications, of Werner's syndrome. About one hundred forty cases of this recessively inherited syndrome have been reported. Most patients become recognizable in their thirties by their short stature, typical facies, premature graying, hair loss, cataracts, atrophy of skin and subcutaneous tissue, and acral sclerosis. Advanced peripheral vascular disease occurs early; angina, skin cancer, diabetes mellitus, and internal malignancy are common. Most patients die before the age of fifty years either from complications of anteriosclerotic vascular disease or malignancy.
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PMID:Werner's syndrome. 735 90

To assess the risk factors for atherosclerosis in Werner's syndrome (WS), coagulation/fibrinolytic system parameters and lipid levels were investigated in 9 non-smoker patients with WS and compared with normal control values (N). The levels of thrombin antithrombin III complex (p < 0.05), D-dimer (p < 0.05), tissue plasminogen activator (p < 0.005) and PA inhibitor 1 (p < 0.01) were significantly increased, while the level of thrombomodulin (p < 0.005) in the fasting plasma was significantly decreased in the WS cases compared with N. Lipid profiles confirmed that 8 of the 9 patients were of hyperlipidemia type IIb, 7 had hyperinsulinemia and 5 fulfilled the criteria for clinical diabetes mellitus. The hypercoagulable condition suggested the existence of multiple risk factors for atherosclerosis in WS in addition to the previously reported hyperinsulinemia and hyperlipidemia.
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PMID:Hypercoagulable state indicates an additional risk factor for atherosclerosis in Werner's syndrome. 749 61

The tissue sensitivity to insulin was evaluated using the hyperinsulinemic euglycemic clamp technique in a 44-year old male with Werner's syndrome associated with diabetes mellitus. In addition, the autophosphorylation of insulin receptors and the number of autophosphorylated insulin receptors were measured in his erythrocytes by a new enzyme-linked immunosorbent assay. He had an increased serum insulin level (30.5 microU/ml) in addition to hyperglycemia (226 mg/dl), suggesting that he had insulin-resistant diabetes mellitus. A clamp study revealed that his insulin-stimulated glucose disposal rate (2.80 mg/kg/min) was comparable to that in noninsulin-dependent diabetes mellitus (4.14 +/- 1.94 (SD) mg/kg/min, n = 23). The number of autophosphorylated insulin receptors per 300 microliters of erythrocytes was also identical to that in normal control subjects. In addition, the autophosphorylation of insulin receptors determined at six different insulin concentrations was within the normal range, even when it was expressed as per 300 microliters of erythrocytes as well as per unit receptor. These results demonstrate that insulin resistance in the patient with Werner's syndrome is caused by a defect that cannot be detected by means employed in this study, and suggest that the defect is present at the steps distal to the autophosphorylation of tyrosine kinase of insulin receptors.
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PMID:Autophosphorylation of insulin receptor in a patient with Werner's syndrome associated with insulin resistant diabetes mellitus. 759 91

Werner's syndrome is characterized by premature aging and frequent impaired glucose tolerance or overt diabetes. Insulin resistance may play an important role and may be caused by a post-receptor defect or dysfunctional insulin receptor. The present study was undertaken to investigate the insulin receptor gene mutation in Werner's syndrome. The genomic DNAs were obtained from four patients with Werner's syndrome. Exons 2-22 of the insulin receptor gene except exon 1 were amplified from genomic DNA by the polymerase chain reaction and screened for nucleotide variation by examining for single-stranded conformational polymorphisms. There were no nucleotide variations in exons 2, 4-->7, 9 and 12-->22. Variants were thus found in exons 3, 8, 10 and 11 and each were sequenced. The variant in exon 8 was due to a silent polymorphism (GAT-->GAC/T, Asp519) and other variants in exons 3, 10 and 11 were caused by nucleotide substitutions in introns. These results suggest that the patients with Werner's syndrome express normal insulin receptors and that the primary genetic lesion for insulin resistance is not in the insulin receptor gene. Insulin resistance in Werner's syndrome is thus likely by a post-receptor defect.
Diabetes Res Clin Pract 1994 Dec 31
PMID:Molecular analysis of insulin receptor gene in Werner's syndrome. 773 97

Werner's syndrome is a rare inheritated disorder characterized by accelerated aging and is often accompanied by diabetes mellitus or impaired glucose tolerance. Previous reports suggest that insulin resistance is involved in the development of diabetes associated with Werner's syndrome. In the present study, CS-045((+/-)-5-[4-(6-Hydroxy-2,5,7,8-tetramethylchroman-2-ylmet hoxy)benzyl] - 2,4-thiazolidinedione, a new oral hypoglycemic agent which reportedly reduces insulin resistance, was administered to 2 Werner's syndrome patients. The patients were hospitalized for the duration of the study. During a pretreatment period lasting 8 weeks the patients received a controlled diet, however, their previous treatment was unchanged. Throughout the 4-week treatment period, each subject's blood glucose level was measured 7 times each day (07:30, 10:00, 11:30, 14:00, 17:30, 20:00, 22:00) for 1 week at 8, 4, and 1 week before treatment and at 2 and 4 weeks after treatment. To assess insulin action, the euglycemic glucose clamp technique was performed in these subjects at insulin infusion rates of 20, 120 and 400 mU/kg/min before and after 4 weeks of treatment. After 4 weeks of treatment with CS-045, the mean blood glucose level at each time point measured in this study was markedly lower compared to the corresponding pretreatment level.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1994 Jul
PMID:Increased insulin responsiveness after CS-045 treatment in diabetes associated with Werner's syndrome. 798 48

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's syndrome is a rare clinical entity and approximately 150 cases have been reported in the medical literature. Werner's syndrome, inherited by autosomal recessive transmission, is characterized primarily by a short stature, premature greying and balding, trophic ulceration of the legs, diabetes mellitus and hypogonadism. These features combine to present a picture of adult progeria. In this brief report we describe a 51-year-old Bedouin male with Werner's syndrome, diagnosed as erythroleukemia (AML-6), and presenting as acute pancytopenia. The patient died two months after diagnosis. This is a rare case of erythroleukemia in a patient with Werner's syndrome. We survey current knowledge of the cytogenetic pathogenesis of Werner's syndrome and erythroleukemia, and attempt to explain the possible link between these two rare syndromes.
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PMID:A patient with Werner's syndrome and erythroleukemia: just coincidence? 917 19

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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