Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreased fatty acid and glucose incorporation into human adipose tissue (FIAT and GLIAT) are frequently found in primary hypertriglyceridemia (HTG) and might also contribute to the defective removal of lipoprotein triglyceride (TG) in non-insulin-dependent diabetes mellitus (NIDDM). To study this possible mechanism, FIAT and GLIAT were determined in needle biopsy specimens from 14 patients with newly diagnosed NIDDM and in 14 age- and weight-matched controls. A patient with insulinoma and hyperinsulinism was also studied. FIAT and GLIAT processes were markedly reduced in patients with NIDDM that developed at the onset of maturity. Insulinoma patients, with normal plasma TG, showed FIAT-GLIAT values in the high to normal range before operation. A direct, highly significant correlation (P less than 0.001) was demonstrated between FIAT and GLIAT in diabetics, insulinoma and controls when considered together. Plasma TG and glucose concentrations were inversely related to FIAT and GLIAT. These relationships were independent of the degree of obesity. It is suggested that impaired FIAT and GLIAT might contribute to defective TG removal and HTG which are often demonstrated in NIDDM.
Atherosclerosis 1982 Mar
PMID:Fatty acid and glucose incorporation into human adipose tissue in non-insulin-dependent diabetes and in insulinoma. Inverse relations with plasma triglyceride and glucose concentrations. 628 88

Clinical hyperproinsulinemia occurs not only in familial hyperproinsulinemia, but also in insulinoma, renal failure, and even in non-insulin-dependent diabetes mellitus (NIDDM). The etiology of hyperproinsulinemia is divided into (1) abnormality of pro-insulin molecules, (2) abnormality of pancreatic beta-cells other than proinsulin molecules, (3) retardation of proinsulin clearance. Hyperproinsulinemia is now thought to be both a result of the above-mentioned diseases and a cause of atherosclerosis in patients with NIDDM. Recent developments in molecular biology have deepened our knowledge of the biosynthesis and role of proinsulin, especially the prohormone sorting mechanism into secretory granules in pancreatic beta-cells.
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PMID:[Etiology and molecular biology of hyperproinsulinemia]. 798 77

Hyperinsulinemia has been assumed to contribute to the pathogenesis of atherosclerosis. To assess the reliability of such claim we planned a retrospective study on a cohort of patients with pancreatic insulin producing neoplasm. A correlation was sought between fasting insulin plasma levels and the metabolic profile emerging from those parameters known to be cardiovascular risk factors, i.e. plasma triglycerides and cholesterol, insulin resistance, hypertension. Special attention was paid to the duration of disease, because the time exposure to hyperinsulinemia could play an important role in developing cardiovascular disease. Seventy patients, 41 females and 29 males, aged 44.9 +/- 1.96 yr (range 15-80), with surgically proved insulinoma were included in the study. Chronic exposure to hyperinsulinemia was documented through the measurement of insulin plasma levels either in the fasting state or post-prandially, resulting in 44.7 +/- 3.28 and 149.9 +/- 12.22 microU/ml, respectively. Fasting glycemia in average was 45.3 +/- 1.34 mg/dl. Plasma triglycerides and cholesterol concentrations were 136.3 +/- 7.93 and 195.8 +/- 5.18 mg/dl, respectively, their distribution overlapping that anticipated for the general population. No correlation arose between the degree of hyperinsulinemia and the lipidic profile. Preoperative blood pressure was 136.9 +/- 2.87 mmHg, systolic and 81.9 +/- 1.32 mmHg, diastolic. Hypertension was present in 5 (7.1%) out of 70 patients and persisted after tumor removal. A condition of insulin resistance (M = 4.06 +/- 0.4 mg/kg min vs 7.41 +/- 0.21) was documented through the euglycemic hyperinsulinemic clamp technique in 20 patients and showed a positive and significant correlation with fasting insulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Absence of clinically overt atherosclerotic vascular disease and adverse changes in cardiovascular risk factors in 70 patients with insulinoma. 814 64

Intracellular protein transport in endothelial cells is selectively inhibited by homocysteine, a thiol amino acid associated with both thrombosis and atherosclerosis. In a previous study, homocysteine decreased cell surface expression of the surface transmembrane glycoprotein thrombomodulin without decreasing secretion of another endothelial cell protein, plasminogen activator inhibitor-1. To define further the effects of homocysteine on protein transport, we examined the processing and secretion of the multimeric glycoprotein von Willebrand factor (vWF) in human umbilical vein endothelial cells. Incubation with 2 mmol/L homocysteine resulted in complete loss of vWF multimers and prevented asparagine-linked oligosaccharide maturation, propeptide cleavage, and secretion; these effects are consistent with impaired exit from the endoplasmic reticulum (ER). Dimerization was only partially inhibited, suggesting that homocysteine causes retention of provWF in the ER without preventing dimer formation. In pulse-chase incubations, intracellular provWF was degraded before exiting the ER in homocysteine-treated cells. Homocysteine also inhibited the processing and secretion of a carboxyl-terminal truncation mutant of human provWF expressed in rat insulinoma cells, indicating that retention in the endoplasmic reticulum can be mediated by regions of provWF apart from the carboxyl-terminal 20-Kd segment. These results suggest that retention of secretory proteins in the ER is regulated by redox mechanisms and imply that the intracellular transport of multiple endothelial cell proteins may be altered in patients with homocystinuria.
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PMID:Homocysteine inhibits von Willebrand factor processing and secretion by preventing transport from the endoplasmic reticulum. 842 60

Autoimmune-target cells in autoimmune disease (AID) are usually construed as constitutionally normal healthy cells. A related assumption is that other cells in the body of AID patients, except for certain immunocytes, are healthy cells. An implication of that view is that any systemic pathology in organ-specific AID is related to metabolic derangements secondary to tissue destruction. However, much data on target and other cells in AID suggest widespread primary cellular defects. In insulin-dependent diabetes mellitus (IDDM), for example, many "complications" such as atherosclerosis, premature arterial stiffening, senescence of fibroblasts in vitro, and exuberant growth of smooth muscle and mesangial cells in vivo are not strictly attributable to glucose elevation. Also unexplained is the similar appearance of IDDM beta-cells and cells from insulinoma and why the prodromal phase of IDDM has many insulinoma-like features. While AID target cells have often been likened to neoplastic cells, investigators have rarely explored the possibility that autoimmunity in AID is fundamentally antineoplastic. This is likely because the dominant ideas in oncology and immunology-somatic mutation and clonal deletion, respectively-have prevented explanations for how normal immunity could detect transforming cells not expressing non-self antigens. New and less conventional theories of cancer and immunity have facilitated such an explanation. I use Rubin's "epigenetic" aging model of carcinogenesis and Matzinger's "danger" model of immunity to integrate the immunological and oncological sides of AID. In particular, I postulate that individuals suffering from AID have inherited many foci of prematurely aging cells. Those inherently damaged cells adapt to in vivo challenges by beginning to transform into cancer cells. However, as long as those stressed cells have not fully transformed, they will continue to signal "danger" to the innate immune system. The clinical outcome of that struggle between incipient neoplasia and immunity will vary depending upon the degree of tumor-proneness and resistance of the individual. Borrowing from cancer geneticist Henry Lynch, I postulate that tumor-resistance is inherited as a quantitative polygenic trait in direct proportion to tumor-proneness. I further contend that tumor-proneness and immunity are linked polygenic traits such that the greater one's tumor-proneness, the more powerful his/her antitumor immunity. I point to the shared DNA repair deficiency of certain cancer-prone syndromes and HLA-linked AID, their occasional co-occurrence, and their demonstrably exceptional immunity against solid tumors. I propose that HLA-linked AID constitute "chronic hypersensitivity syndromes" due to immunity's largely hidden battle to suppress multiple incipient neoplastic microfoci. Much of the physiopathology of AID is explicable as a sustained systemic response to threatened neoplastic transformation.
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PMID:Hypothesis. Bystanders or bad seeds? Many autoimmune-target cells may be transforming to cancer and signalling "danger" to the immune system. 1126 91