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

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

We studied histamine metabolism, i.e., histidine decarboxylase (HD)-mediated synthesis and histaminase-mediated catabolism, in relation to intracellular histamine content in both aortic endothelial and subjacent smooth muscle cells of control and diabetic rats. Diabetes was induced by a single jugular vein injection of streptozotocin (55 mg/kg in acidified saline, pH 4.5), and animals were held for either 2 or 4 weeks following overt manifestation of diabetes. An additional 4-week diabetic group received insulin (Iletin NPH, 10 U per 24 hour) during the last week. With respect to control values, the histamine content of aortic endothelial cells increased 138%, HD activity increased 250%, and histaminase activity decreased 50% over the 4-week period. In subjacent smooth muscle cells, the histamine content increased in excess of 150%, HD activity increased more than 300%, and histaminase activity decreased in excess of 30%. Insulin treatment for the last week resulted in complete reversal of all these changes. These results support the concept that a large vessel response similar to the microcirculatory prolonged phase of inflammation occurs in experimental diabetes, a change similar to that occurring in experimental atherosclerosis. They also indicate that both synthetic and catabolic changes occur in histamine metabolism under these conditions, changes that alter arterial wall histamine pools, and suggest that insulin administration under conditions of experimental diabetes may modulate aortic histamine metabolism and the resultant intraaortic histamine pools.
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PMID:Aortic endothelial and smooth muscle histamine metabolism in experimental diabetes. 680 15

To investigate the effects of hyperinsulinemia on the myocardial vessels, long acting insulin (mixtard, a combination of 30% regular human insulin and 70% NPH human insulin) was injected daily for 8 weeks, intraperitoneally, in two strains of rats, normotensive WKY and hypertensive SHR. There were four groups in all, a control group, and an insulin-injected group in each strain. The drinking water contained 10% glucose to prevent hypoglycemia in the insulin-injected rats. At the end of the 8 weeks experimental period, after measuring blood pressure and taking blood for the determination of glucose, urea, creatinine, and insulin, the rats were killed. The organs were fixed in formaldehyde. The blood glucose levels were higher at the end of the experiment, in both the placebo- (saline)-injected and the insulin-injected rats. Blood pressure rose significantly only in the insulin-injected SHR. The intramyocardial arterioles in the insulin-injected SHR had a significantly thicker vascular wall than the placebo-injected SHR, as represented by the vessel wall to lumen ratio, because of hypertrophy of the media. When compared with the placebo injected WKY rats, there was a higher wall/lumen ratio of the intramyocardial arterioles in the insulin-injected WKY, but the difference did not reach significance. Heart weights factored by body weights was significantly higher in insulin-injected as compared with placebo-injected SHR. Myocardial infarctions were observed in four of eight rats in the insulin-injected SHR group despite the fact that there were no signs of atherosclerosis or intimal thickening. It is possible that the increase in heart weight and the probable increase in metabolic activity resulting from hyperinsulinemia, together with the increased oxygen demand of the myocardium and the arteriolar narrowing, may have contributed to the occurence of myocardial infarctions in the absence of atherosclerotic coronary occlusion.
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PMID:Hyperinsulinemia induces myocardial infarctions and arteriolar medial hypertrophy in spontaneously hypertensive rats. 919 11

In this prospective study we aimed to compare insulin plus acarbose with insulin plus gliclazide with respect to their effect on insulin requirement, lipid profiles and body mass index (BMI) while achieving good glycemic control. Forty patients with type 2 diabetes mellitus who were on conventional insulin therapy (subcutaneous insulin therapy consisting of regular and NPH insulin, two times a day) were included in the study. They were randomized to double blind treatment with insulin in combination with gliclazide or acarbose for 6 months. For both groups, acceptable glycemic control was achieved at the end of study period. The mean HbA(1c) levels decreased from 8.32+/-0.26 to 7.13+/-0.18% in acarbose group and 8. 6+/-0.15 to 7.48+/-0.21% in the gliclazide group. The difference between groups was not significant (P 0.29). In the acarbose group, total cholesterol and LDL concentration decreased significantly while other parameters did not change. In the gliclazide group, HDL levels decreased significantly from 46.6+/-2.48 mg/dl to 41.3+/-2.09 mg/dl (P 0.001) BMI increased significantly from 27.60+/-1.21 kg/m(2) to 28.69+/-1.26 kg/m(2). (P 0.003) Total daily insulin dose was not changed in the acarbose group significantly, but increased from 42.6+/-2.73 to 49.27+/-3.58 U/day, which was significant in gliclazide group of (P 0.016). In the acarbose group, there were no significant differences between responders and nonresponders with respect to fasting and stimulated C-peptide, HbA(1c) levels and baseline BMI values. But in the gliclazide group, baseline BMI values were significantly higher in the nonresponding group compared to responders (P 0.02). In conclusion, combination of insulin with acarbose can be a good alternative for type 2 diabetic patients on insulin therapy; seems more beneficial than combination with gliclazide; may have advantage of achieving good glycemic control without increasing insulin dose and BMI; also may have the advantage of providing a decrease in LDL level, which are all important to prevent atherosclerosis.
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PMID:Effects of combination of insulin and acarbose compared with insulin and gliclazide in type 2 diabetic patients. 1043 59