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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin-induced diabetic rats show a marked fasting hypertriglyceridemia. It appears that only the very low density lipoprotein (VLDL) fraction is increased. VLDL from either normal or diabetic rats was labelled in vivo in the triglyceride moiety with [3H]palmitate and isolated. Both preparations, if injected intravenously into recipient rats, are removed more slowly from the circulation of diabetic rats as compared to normal rats, resulting in a reduction of the fractional catabolic rate (F.C.R.) by 70%. However, the absolute catabolic rate (turnover) of VLDL triglycerides was not changed in diabetics. It is concluded that the hypertriglyceridemia of the the diabetic rat is caused by a defective removal mechanism of VLDL triglycerides. The F.C.R. of 125I-labelled low density lipoproteins and high density lipoproteins is only 1-3% of the value for VLDL triglycerides and unchanged in diabetic rats.
Atherosclerosis 1977 Jan
PMID:Hypertriglyceridemia in the diabetic rat. Defective removal of serum very low density. 18 77

The present study has indicated that significant shifts in plasma, urinary, and tissue taurine and in non-taurine dialyzable amines occur in the STZ-induced diabetic rat, especially in the kidney. Taurine administration at relatively low dosage ameliorated only kidney taurine concentration. Anticipated alterations in plasma glucose and creatinine were observed but neither of these changes was affected by taurine administration. Similarly, urinary output of creatinine, glucose, and NAG increased significantly among diabetic rats, but none of these were detectably influenced by taurine. Increases in plasma triglycerides observed in STZ-induced diabetes appear to be attenuated by taurine administration, and although cholesterol concentrations were lower in taurine-treated rats, the differences were not statistically significant. These findings should encourage further studies of these effects in rats as a useful model for several complications of human diabetes including atherosclerosis, retinopathy, and nephropathy.
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PMID:Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides. 231 Jun 8

The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as well as for the initiation and progression of diabetic nephropathy are not fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been invoked in the former and thromboxane (TXB2) and hyperlipidemia in the latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid synthesis and serum lipid profiles. We therefore examined the effects of a FO-enriched diet on glomerular filtration (GFR), proteinuria, glomerular eicosanoid production, and serum lipids in rats with streptozotocin-induced DM (STZ-DM). Groups of 5-8 rats with STZ-DM were maintained on low insulin and then pair-fed with isocaloric diets enriched with either FO (20% w/w) or beef tallow (BT; 20% w/w). GFR was determined in the same animals at onset of diet and after 8 and 20 weeks on the respective diets by [14C]inulin clearance using implanted osmotic minipumps each time. Significant hyperfiltration was present initially and GFR did not change on either diet for 20 weeks, in spite of a significant and greater than 50% decrease in all prostaglandins (PGE2, TXB2, PGF2 alpha, 6-keto, PGF1 alpha) produced by glomeruli isolated from DM/FO as compared to DM/BT or control rats. FO diet completely corrected the hypertriglyceridemia of diabetes and significantly reduced the mild and early proteinuria of DM. The decrease in proteinuria and the correction of hyperlipidemia of DM by a FO-enriched diet may be beneficial in the long term not only for the development of diabetic glomerulopathy, but also for the accelerated atherosclerosis of DM.
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PMID:Effects of fish oil on glomerular function in rats with diabetes mellitus. 240 55

Diabetes is associated with a dramatic increase in the risk of thrombotic and atherosclerotic disease. The underlying factors responsible for this predisposition as well as the mechanisms involved have yet to be elucidated. Two endogenous substances, prostacyclin (PGI2) and thromboxane (TXA2), have recently been shown to possess significant vascular and thrombotic activity and are known to be altered in atherosclerosis, thrombotic conditions, and diabetes. We determined the conversion of 14C-arachidonic acid (AA) to PGI2 and TXA2 by lungs, aortas, and platelets obtained from chemically induced diabetic rats. In addition, we investigated the ability of insulin or tolbutamide to reverse these changes. Streptozotocin (STZ)-injected rats developed blood glucose levels 2-4 times that seen in normoglycemic controls. Intact perfused lungs isolated from rats beginning 7 days after STZ treatment synthesized 22-30% less PGI2 from 14C-AA. The ratio of PGI2/TXA2 was decreased in the diabetic rat lungs and was inversely proportional to plasma glucose levels at the time of death. Platelet TXA2 generation was increased 67% above control in diabetic rats while aortic PGI2 generation was decreased 28% below normoglycemic controls. Ten-day treatment with NPH insulin 20 U/kg s.c. in STZ-pretreated rats lowered plasma glucose toward normoglycemia more effectively than tolbutamide 200 mg/kg orally. Partial correction of the decreased pulmonary PGI2/TXA2 ratio seen in diabetic rats was produced by insulin and tolbutamide in proportion to their ability to lower blood glucose. At the doses employed, insulin caused aortic PI2 and platelet TXA2 generation from 14C-AA to approach that seen in mormoglycemic controls more effectively than tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impact of insulin or tolbutamide treatment on 14C-arachidonic acid conversion to prostacyclin and/or thromboxane in lungs, aortas, and platelets of streptozotocin-induced diabetic rats. 635 92

1. There is evidence to suggest that adenosine may regulate arterial smooth muscle cell (SMC) growth and proliferation, which is a key event in atherogenesis. This regulation may be mediated via adenylate cyclase. As diabetes is a known risk factor for atherosclerosis, we investigated the growth of aortic SMC from diabetic rats in primary culture and their sensitivity to adenosine and to adenylate cyclase activity. 2. Diabetes was induced with streptozotocin (STZ, 66 mg kg-1, i.p.) Aortic SMC primary cultures were prepared from STZ-diabetic and age-matched rats 5 weeks after the STZ injection. 3. SMC from STZ-diabetic rats grew faster and reached greater densities at confluence than those from non-diabetic animals. 4. Adenosine inhibited growth in both control and diabetic SMC. However, cells from STZ-diabetic rats were apparently more sensitive to adenosine. 5. Direct activation of adenylate cyclase by forskolin induced a dose-dependent growth inhibition, similar in both groups of cells. 6. Cholera toxin, an activator of stimulatory GTP-binding protein (Gs), induced a similar growth inhibitory response in non-diabetic and diabetic SMC. Pertussis toxin (PTX), an inactivator of inhibitory GTP-binding protein (Gi), did not itself affect SMC growth. However, PTX increased dose-dependently the growth inhibition induced by adenosine in SMC from non-diabetic rats but not in SMC from diabetic rats. 7. These findings suggest a functional abnormality in Gi activity in SMC from diabetic rats, that would explain the increased sensitivity to the nucleoside. This impaired inhibitory pathway may reflect changes in the growth regulation of SMC in experimental diabetic states.
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PMID:Adenosine inhibitory effect on enhanced growth of aortic smooth muscle cells from streptozotocin-induced diabetic rats. 876 8

Glycoxidation reactions lead to the formation of permanent, irreversible chemical modifications and cross-links in protein, such as the glycoxidation products carboxymethyllysine (CML) and pentosidine. It has been implicated that CML as well as Amadori products play a role in the formation of superoxidative products, such as H2O2 and advanced glycosylation endproducts in trapping LDL. Therefore, a possible relationship between glycoxidation and lipoperoxidation might exist because oxidized lipoprotein, which has been directly linked to atheroma formation, could be produced by the superoxidative products released from the pathway of CML formation. Using a CML-specific monoclonal antibody (6D12) and a specific antiserum against hexitol-lysine (HL), an Amadori product, we studied the relationship between glycoxidation and lipoperoxidation by determining the aortic CML contents with ELISA and the fluorescence levels of lipoperoxidation side products, malondialdehyde (MDA) and hydroxynonenal (HNE) from STZ-induced diabetic rats and age-matched control rats. The immunohistochemical and ultrastructural changes relevant to glycoxidation and lipoperoxidation were also studied. The CML content measured by ELISA in DM rats was significantly higher than that in the control rats at 28 weeks (n = 11, P < 0.01). The levels of MDA-linked and HNE-linked fluorescence in the DM rats increased in a similar way and were significantly higher than the levels in control rats at 28 weeks (n = 11, both P < 0.01 at 28 weeks). The CML contents correlated with the fluorescence levels of both MDA-linked (n = 19, r = 0.638, P < 0.01) and HNE-linked fluorescence (n = 19, r = 0.629, P < 0.01) only in the DM rats, but not in the control rats. Our immunohistochemical study thus demonstrated that CML was initially formed in the aortic media of diabetic rats in the 16th week of diabetes, localized primarily in the extracellular matrix surrounding the aortic smooth muscle cells after HL occurred early in the 2nd week of diabetes. Consequently, a significant increase in the extracellular matrix and decrease in the area of the SMCs were observed in the aortic media in the DM rats by a morphometrical study. The in vivo results of this study provided the first evidence that CML correlated with fluorescence levels of MDA and HNE, and thus suggested the existence of a close relationship between glycoxidation and lipoperoxidation in vivo. This information is thus considered to shed some new light on the etiology of atherogenesis in diabetes.
Atherosclerosis 1998 Feb
PMID:Glycoxidation in aortic collagen from STZ-induced diabetic rats and its relevance to vascular damage. 954 7

Epidemiological studies have established that diabetes mellitus and hypertension are independent risk factors for atherosclerosis. One of the earliest abnormalities seen in atherogenesis is enhanced monocyte adherence to the endothelium. The mechanisms by which diabetes mellitus or hypertension enhances monocyte-endothelial cell interactions are incompletely characterized. It is not known whether there are additive interactions between these risk factors on endothelial adhesiveness for monocytes. Male Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were fed a normal or fructose-enriched diet. In some cases, animals were injected with streptozotocin (35 mg/kg body weight) to induce diabetes. After 2 weeks, plasma was drawn for biochemical measurements, and thoracic aortas were harvested, opened longitudinally, and exposed to fluorescently labeled mouse monocytoid cells (WEHI 78/24, 2 x 10(6)/mL) for 30 minutes on a rocking platform. Adherent cells were counted by epifluorescence microscopy. WEHI 78/24 binding to aortic segments from SHR animals was elevated compared with segments from WKYs. Fructose feeding alone had no effect on endothelial adhesiveness. When WKYs were made hyperglycemic by STZ injection, monocyte binding was 160% of the control value. Elevated monocyte binding was also observed in aortas derived from SHR animals injected with STZ, indicating an additive effect of hypertension and hyperglycemia. To determine whether alterations in oxidative state played a role in the endothelial adhesiveness, aortic segments were exposed to lucigenin (250 micromol/L) for measurement of superoxide anion. Aortic segments from SHR elaborated 120% more superoxide anion than did controls. Elevated free-radical production was also observed in aortas from diabetic WKYs. Furthermore, thoracic aortas derived from diabetic SHR animals elaborated more superoxide anion than did any of the other groups (374%, P<0.05). Immunohistochemical staining for monocyte chemotactic protein-1 demonstrated increased expression in aortas isolated from diabetic WKY and SHR compared with control vessels. These studies demonstrate that both diabetes and hypertension lead to increased monocyte adherence to the endothelium. This abnormality is associated with increased vascular superoxide production and monocyte chemotactic protein-1 expression. Furthermore, there appears to be an additive interaction between hyperglycemia and hypertension in their effects on endothelial adhesiveness and its determinants.
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PMID:Interaction of diabetes and hypertension on determinants of endothelial adhesiveness. 963 36

Diabetes mellitus confers a threefold to fivefold increased risk of mortality from vascular disease. The primary cause of this increased incidence of vascular disease is atherosclerosis, but the mechanisms accounting for the increase are unclear. Chronic hyperglycemia is a common feature of all forms of diabetes mellitus and may contribute greatly to the increased incidence of atherosclerosis, via promotion of both lipoprotein and tissue glycation, which may have atherogenic effects. The present study investigated the effect of chronic hyperglycemia on measures of low-density lipoprotein (LDL) metabolism and atherosclerosis in streptozotocin-induced diabetic (STZ-DM) and control cynomolgus monkeys after 6 months of study. Consistent with a chronic hyperglycemic state, diabetic monkeys had significant increases in glycated hemoglobin (GHb) and glycated plasma LDL concentrations, but had minimal changes in total plasma cholesterol (TPC) or triglyceride (TG) concentrations during the study. Forty-eight hours before necropsy, control and in vitro-glycated LDL were differentially radiolabeled and coinjected into diabetic and control monkeys. There was a significant increase in arterial LDL accumulation in femoral arteries from diabetic monkeys compared with controls, with similar trends in other arterial sites. The effect of LDL glycation on arterial LDL accumulation was minimal in both groups. Arterial segments from diabetic monkeys also had greater amounts of arterial cholesterol content compared with controls. Histomorphometric analyses showed that diabetic monkeys had significantly greater intimal areas in the femoral artery and abdominal aorta compared with controls. Diabetic monkeys also had reduced arterial remodeling, or compensation, in the femoral artery and abdominal aorta. However, there was no difference in advanced glycation end products (AGE) in arterial collagen between groups. In conclusion, experimentally induced diabetes mellitus increases arterial LDL accumulation and atherosclerosis extent in cynomolgus monkeys before changes in AGE formation. The increased atherogenesis may be due to changes in lipoproteins or direct effects of hyperglycemia on the artery wall.
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PMID:Chronic hyperglycemia increases arterial low-density lipoprotein metabolism and atherosclerosis in cynomolgus monkeys. 971 90

Type I diabetes is associated with a unique form of cardiomyopathy in the absence of atherosclerosis. The mechanisms involved in this phenomenon are not defined, but in humans this is associated with initial diastolic dysfunction followed by altered contractile performance. A relevant animal model would provide opportunities for mechanistic studies and experimental therapeutics, but none have been previously established for this unique form of cardiac pathophysiology, particularly with respect to clinically relevant and time-dependent diastolic and systolic assessments. Here we tested the hypothesis that the streptozotocin rat model mimics human phenomena with respect to time-dependent diastolic and systolic performance deficits, and investigated a role for cardiac hypertrophy and/or fibrosis. Streptozotocin was dosed 65 mg/kg i.p. and cardiac performance was assessed longitudinally for 56 days using noninvasive echocardiographic techniques. Significant hyperglycemia was detected within 3 days and remained elevated throughout the study (p<0.05). Significant reductions in HR and diastolic performance (transmitral flow velocities and slopes) were observed within 3 days relative to age matched controls, and these reductions progressed throughout the 56 day study. In contrast, statistically significant systolic dysfunction (LV fractional shortening, cardiac output) and LV dilation were detected only after 35 days. Increases in LV size and/or extent of fibrosis were not observed at any time. These results demonstrate the value of echocardiographic methods for time-dependent diastolic and systolic assessments in rodent models. Furthermore, diastolic dysfunction precedes contractile abnormalities in the streptozotocin model, similar to events that occur in humans.
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PMID:Diabetes related cardiomyopathy time dependent echocardiographic evaluation in an experimental rat model. 1151 Sep 48

Chronic intraperitoneal or subcutaneous insulin administration increases triglyceride secretion rate (TGSR) in normal rats. We wished to determine the effect of this treatment on TGSR and the hepatic lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in diabetic rats. Streptozotocin-diabetic rats, untreated (D), diabetic rats treated with insulin (3 U/day for 21 days) intraperitoneally (IP) or subcutaneously (SC) and non-diabetic rats (N) were studied. TGSR was determined using Triton WR-1339. Fasting glucose and triglyceride levels, high in D, were normalized by insulin treatment regardless of route. Peripheral insulin levels were lowest in D and highest in SC, portal insulin levels were lowest in D and highest in IP. Non-esterified fatty acid levels were not elevated in D, presumably due to adipose tissue depletion. TGSR was reduced in D (P<0.05) and was normalized following insulin administration, regardless of route. ACC activity was normal, but FAS was decreased in D (P<0.05). ACC and FAS were normal in both IP and SC. Thus, in streptozotocin-diabetic rats, chronic intraperitoneal or subcutaneous insulin treatment increases TGSR and FAS activity from their low levels in insulin-deficient rats to levels equal to but not higher than those in normal rats.
Atherosclerosis 2002 Apr
PMID:The effect of chronic insulin delivery via the intraperitoneal versus the subcutaneous route on hepatic triglyceride secretion rate in streptozotocin diabetic rats. 1188 17


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