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)

Vascular disease in diabetics could arise in part from altered vessel wall catebolism. Specific activities of hydrolases in aortic smooth muscle cells from rats with streptozotocin-induced diabetes were measured. Enyzmes included: neutral alpha-glucosidase, alpha-mannosidase, and lysosomal N-acetyl beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 4,8, and 11 weeks of diabetes, activities of all enzymes studied were decreased significantly in diabetic vessels, decreases ranging from 15% for cathepsin C to 62% for alpha-mannosidase. After 3 weeks of diabetes, insulin treatment for 1 week restored enzyme levels to normal. After 7 weeks of diabetes, 1 week of insulin treatment did not restore enzyme levels fully to normal (acid cholesteryl esterase was unchanged); 4 weeks of insulin did. Acid phosphatase and N-acetyl beta-glucosaminidase activities were reduced markedly in histochemical studies of diabetic aortas at all time periods and were restored by insulin treatment. Alloxan-induced diabetes gave results similar to those with streptozotocin. Significant decreases of aortic hydrolase activities, including those of lysosomes, occur in experimental diabetes mellitus and could contribute to accumulation of substrates in vascular smooth muscle cells.
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PMID:Hydrolase activities in the rat aorta. I. Effects of diabetes mellitus and insulin treatment. 14 80

Hypertension is an important risk factor for atherosclerosis and often occurs in association with diabetes mellitus. Specific activities of hydrolases in homogenates of aortas from rats with renal-clip hypertension, normotension following a period of hypertension, and hypertension combined with streptozotocin-induced diabetes mellitus were measured. Enzymes included: neutral alpha-glucosidase, and lysosomal N-acetyl-beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase. Six weeks of normotension following 6 weeks of hypertension resulted in restoration to normal of four of the six enzyme activities; the remaining two enzymes were significantly below normal levels. Combined hypertension and diabetes mellitus showed smooth muscle cell levels of four of the five hydrolases measured to be significantly lower than those present with hypertension alone. In every instance, histochemical studies of aortas showed acid phosphatase and N-acetyl-beta-glucosaminidase activities which corresponded to the biochemical findings. These findings indicate profound and discrete effects of two clinical risk factors on vascular smooth muscle cell lysosomes.
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PMID:Hydrolase activities in the rat aorta. II. Effects of hypertension alone and in combination with diabetes mellitus. 65 43

The change of acid cholesteryl ester hydrolase activity in mononuclear leukocyte following treatment of diabetes mellitus was studied in 21 patients with non-insulin-dependent diabetes mellitus (NIDDM). Enzyme activity before treatment in the patients was significantly lower than that in 14 age-matched healthy subjects (1.20 +/- 0.15; mean +/- S.E. vs. 2.20 +/- 0.17 nmol/mg protein/h, P less than 0.01). Enzyme activity before treatment in the patients was significantly increased (P less than 0.05) after 4-8 weeks of treatment. However, enzyme activity of 1.43 +/- 0.14 nmol/mg protein/h observed after treatment in the patients was significantly lower (P less than 0.01) than that in the healthy subjects. There was a significant negative correlation between enzyme activity before treatment and the increase in enzyme activity following treatment (rs = -0.555, P less than 0.01, n = 21). These results indicate that low level of enzyme activity may be insufficiently improved by the treatment of diabetes, and the risk for the development of atherosclerosis as viewed from the enzyme activity may persist even after the treatment in NIDDM.
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PMID:Acid cholesteryl ester hydrolase activity of mononuclear leukocytes in patients with non-insulin-dependent diabetes mellitus: studies before and after treatment of diabetes. 163 50

Acid cholesteryl ester hydrolase activity of mononuclear leukocytes was measured in 52 Type 2 (non-insulin-dependent) diabetic patients. Enzyme activity was significantly lower in the diabetic patients than in 14 age-matched control subjects (0.89 +/- 0.08 (mean +/- S.E.) vs. 2.20 +/- 0.17 nmol/mg protein/hr, p less than 0.01). In diabetic patients undergoing diet treatment only, the enzyme activity was significantly lower in poorly controlled patients than in well controlled patients (0.43 +/- 0.03 vs. 1.15 +/- 0.24 nmol/mg protein/hr, p less than 0.01). In the diabetic patients, there was a significant negative correlation between the enzyme activity and serum total cholesterol or low density lipoprotein cholesterol level (r = -0.361, p less than 0.01, n = 52 or r = -0.630, p less than 0.01, n = 28). These results suggest that a low level of acid cholesteryl ester hydrolase activity in mononuclear leukocyte might play an important role in the progression of atherosclerosis in Type 2 diabetes.
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PMID:Acid cholesteryl ester hydrolase activity of mononuclear leukocyte in type 2 (non-insulin-dependent) diabetic patients. 238 65

We examined the activities of intestinal acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol esterase, enzymes regulating cholesterol absorption, in rats with streptozocin-induced diabetes (STZ-D) to clarify the effect of diabetes on cholesterol absorption. Three weeks after the induction of diabetes, plasma cholesterol levels were slightly but significantly increased in diabetic rats compared with control animals, whereas a far more remarkable increase in plasma cholesterol was observed in diabetic rats when fed an atherogenic diet containing 1% cholesterol, 0.5% cholic acid, and 5% lard. Microsomal ACAT activity in intestinal mucosa was three times higher in diabetic than in control rats. However, no significant difference in the enzyme activity could be detected between diabetic animals fed control chow and those fed the atherogenic diet. Furthermore, insulin supplementation given to diabetic rats caused a reduction of enzyme activity to the levels found in control animals. In contrast, cholesterol esterase activity in rat intestinal mucosa was unaffected by either the induction of diabetes or the atherogenic diet feeding. In conclusion, we disclosed that apparent ACAT activity in intestinal mucosa is elevated in STZ-D rats. Therefore, we postulate that enhancement of CoA-dependent cholesterol esterification in the intestine might be one of the major factors responsible for hypercholesterolemia in diabetes.
Diabetes 1988 Mar
PMID:Increased activity of intestinal acyl-CoA: cholesterol acyltransferase in rats with streptozocin-induced diabetes and restoration by insulin supplementation. 296 15

The effect of insulin on lysosomal acid cholesterol ester hydrolase activity was studied in liver, heart and fat pad preparations from rats and mice. Hyperinsulinemia was induced for a period of 6 days in rats by the subcutaneous administration of exogenous insulin by an osmotic minipump. The effect of more chronic endogenous hyperinsulinemia was studied using genetic strains of diabetic (db/db) mice at 12 weeks of age. Mouse liver and heart preparations were characterized as having an acid pH optimum of 4.5-5 for cholesterol ester hydrolase activity; a smaller but distinct pH optimum could also be observed at pH 7. In contrast, hydrolase activity in mouse fat pad preparations had only one distinct pH optimum of 6.5. Hyperinsulinemia in rats and mice resulted in a significant decrease in acid cholesterol ester hydrolase activity in heart preparations, but had no consistent effect on acid hydrolase activity observed in liver and fat pad preparations. This decrease in lysosomal acid cholesterol ester hydrolase activity in cardiac tissue due to hyperinsulinemia cannot be related to any changes in lipoprotein turnover caused by insulin or diabetes.
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PMID:Effect of hyperinsulinemia on acid cholesterol ester hydrolase activity in liver, heart and epididymal fat pad preparations from rats and mice. 675 44

Insulin deficiency as seen in insulin-dependent diabetes mellitus causes an activation of lipolysis in adipose tissue that results in hydrolysis of stored triglycerides and release of large amounts of fatty acids into the plasma, leading to diabetic ketoacidosis (DKA). Hormone-sensitive lipase (HSL) is thought to be the rate-limiting enzyme of lipolysis in adipose tissue. This study was designed to examine the effects of insulin deficiency on the regulation of HSL in isolated adipocytes. Insulin deficiency was induced by a single dose of streptozotocin. After 8 days, some animals were treated with insulin, and all animals were killed 10 days after induction of insulin deficiency. Compared with levels in control rats, 10 days of insulin deficiency increased HSL activity twofold (P < .05), as assayed for neutral cholesterol esterase activity, and insulin treatment returned HSL activity to normal. HSL protein was increased twofold (P < .05) in streptozotocin-induced diabetic rats, as estimated by immunoblotting, but remained elevated after insulin treatment. Levels of HSL mRNA assessed by Northern blot analysis also increased twofold (P < .01) in adipose cells isolated from streptozotocin-induced diabetic rats, and remained elevated after insulin treatment. In conclusion, our studies suggest that 10 days of insulin deficiency increases HSL expression via pretranslational mechanisms and short-term insulin treatment returns HSL activity to normal via posttranslational mechanisms in adipose tissue.
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PMID:Regulation of hormone-sensitive lipase in streptozotocin-induced diabetic rats. 747 23

Diabetes was induced in rats by the intravenous administration of streptozotocin (STZ; 60 mg/ml). The activity of cholesterol esterase (CEase) in various tissues was determined by use of either a fluorogenic or radioactive substrate. Significant CEase activity was detected in extracts of pancreas. The specific activity of pancreatic CEase was considerably greater in pancreatic extracts from diabetic rats compared with normal rats. The activity of pancreatic CEase increased 6 d after the injection of STZ, but the difference was not statistically significant. It reached a maximum value approximately twice that of normal pancreas at 30 d with statistic significance. The highest specific activity of pancreatic CEase was found in the cytosolic fraction from diabetic rats, whereas the specific activity of the enzyme was lowest the same fraction from normal rats.
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PMID:Enhanced cholesterol esterase activity in the pancreas of rats with streptozotocin-induced diabetes. 800 Mar 71

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.
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PMID:Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. 1101 3

Leptin is produced in adipose tissue and acts in the hypothalamus to regulate food intake. However, recent evidence also indicates a potential for direct roles for leptin in peripheral tissues, including those of the immune system. In this study, we provide direct evidence that macrophages are a target tissue for leptin. We found that J774.2 macrophages express the functional long form of the leptin receptor (ObRb) and that this becomes tyrosine-phosphorylated after stimulation with low doses of leptin. Leptin also stimulates both phosphoinositide 3-kinase (PI 3-kinase) activity and tyrosine phosphorylation of JAK2 and STAT3 in these cells. We investigated the effects of leptin on hormone-sensitive lipase (HSL), which acts as a neutral cholesterol esterase in macrophages and is a rate-limiting step in cholesterol ester breakdown. Leptin significantly increased HSL activity in J774.2 macrophages, and these effects were additive with the effects of cAMP and were blocked by PI 3-kinase inhibitors. Conversely, insulin inhibited HSL in macrophages, but unlike adipocytes, this effect did not require PI 3-kinase. These results indicate that leptin and insulin regulate cholesterol-ester homeostasis in macrophages and, therefore, defects in this process caused by leptin and/or insulin resistance could contribute to the increased incidence of atherosclerosis found associated with obesity and type 2 diabetes.
Diabetes 2001 May
PMID:Insulin and leptin acutely regulate cholesterol ester metabolism in macrophages by novel signaling pathways. 1133 38


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