Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0020473 (hyperlipidemia)
15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent work in our laboratory has shown that oral administration of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia in rabbits. The present experiments were conducted to elucidate the mechanism of TPTF-induced hypertriglyceridemia in rabbits by a combined biochemical and ultrastructural approach. After a single TPTF administration, fasting blood glucose and plasma triglyceride levels increased significantly (P less than 0.02) for about 20 days. On the other hand, both plasma and adipose tissue lipoprotein lipase (LPL) activity was markedly decreased (P less than 0.001) during this period, and triglyceride production rates on day 2 after TPTF administration was significantly decreased (P less than 0.01). Density-gradient ultracentrifugation showed a remarkable accumulation of chylomicron and VLDL in the composition of plasma lipoproteins. Insulin injection to the hypertriglyceridemic rabbits induced a significant recovery of the decreased plasma LPL activity with a concomitant decrease of plasma triglyceride levels, while abeyance of insulin injection resulted in a decrease of LPL activity again. A significant inhibition of insulin release in response to the loading of glucose, glucagon, or arginine was observed in the TPTF rabbits (P less than 0.02). Inhibition of glucagon release was also observed in the arginine-loading test (P less than 0.01). Electron microscopic studies showed small abnormalities in the pancreatic islets of TPTF-treated rabbits. These findings suggest that TPTF inhibits insulin release from rabbit islets, subsequently inducing diabetic lipemia due to the insulin deficiency. Furthermore, it is possible to provide a new animal model for diabetes and diabetic lipemia by administration of TPTF to rabbits.
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PMID:Triphenyltin fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic lipemia by inhibiting insulin secretion from morphologically intact rabbit B-cell. 703 Aug 27

Various sources of food fibers (FF) were compared for efficacy in correction of carbohydrate and lipid metabolism disorders induced by diabetes mellitus type II (DM). The diet containing citrus pectin (CP), wheat bran (WB), lignin-enriched bran (LEB), cellulose pulp (CP) was given to 100 diabetics with hyperlipidemia. Follow-up measurements were made of basal and aftermeal glycemia, cholesterol and triglycerides, immunoreactive insulin and glucagon levels in the serum of the patients before and after 4-week dietetics. The results showed a hypocholesterolemic effect of CP and hypoglycemic effect of WB. The findings urge differentiated use of FF when correcting carbohydrate and lipid metabolism in patients with DM type II.
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PMID:[Comparative efficiency of various food fibers in the correction of carbohydrate and lipid metabolism in patients with type II diabetes mellitus]. 797 42

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.
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PMID:Acute pancreatitis: a multisystem disease. 804 85

In the present study the influence of low doses of intravenous nicotine administration on hormonal and metabolic events was studied in man in view of the clinical implications of moderate smoking on the development of hyperlipidemia. Hormonal, metabolic and cardiovascular effects of a 30 min intravenous nicotine infusion (0.25 or 0.5 microgram/kg/min) were determined in seven non-smoking, healthy, normal weight male individuals after an overnight fast. Nicotine caused a significant dose-dependent increase in the plasma levels of nicotine, cotinine, noradrenaline, adrenaline, glycerol and free fatty acids (FFA). The serum nicotine concentrations peaked at the end of the infusion followed by a gradual decline, although they were still increased 90 min after cessation of infusion. Serum cotinine levels (the main nicotine metabolite) continuously increased during the experiment and statistically significant increases were found from 30 min after the start of infusion of nicotine. Serum noradrenaline, adrenaline, glycerol and FFA levels had increased significantly by 15 min of nicotine infusion. Nicotine produced significant elevations of adrenaline, glycerol and FFA concentrations at both doses (maximal increments of 247, 184 and 153%, respectively) and the peak effect occurred at 30 min. However, noradrenaline levels only responded to the high nicotine dose and the maximal increment (168%) was already found at 15 min. The increments of noradrenaline and adrenaline failed to elicit changes in systolic and diastolic blood pressure or heart rate. Nicotine did not alter plasma levels of glucagon, insulin, glucose, pyruvate or lactate and a non-significant increase in serum cortisol and growth hormone levels was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in circulating lipid and carbohydrate metabolites following systemic nicotine treatment in healthy men. 811 70

Diabetes mellitus with its resulting derangement of various metabolic fuels, carbohydrates, amino acids, lipids, and ketones has the potential to adversely affect the developing fetus. Therefore, strict glycemic control in pregnancy has become the standard of care in modern obstetrics. A considerable amount of research has been undertaken into the metabolic changes that occur during pregnancy in both women with insulin-dependent diabetes and gestational diabetes. This paper will review current research in normal and diabetic pregnancies both in the fasting and fed states as well as during episodes of hypoglycemia. In normal pregnancy insulin secretion increases throughout gestation whereas peripheral insulin sensitivity is decreased. Fasting levels of plasma glucose are reduced by approximately 10 per cent during the first trimester. Maternal amino acid levels are also reduced in normal pregnancy, although cholesterol and triglyceride levels are increased, most dramatically in the second trimester. As gestation advances, progressively increasing amounts of insulin antagonistic hormones are secreted by the placenta. This leads to gestational diabetes in 2 to 3 per cent of women who exhibit hyperglycemia despite an increased insulin response to oral glucose as well as an increased insulin/glucagon ratio. In insulin dependent diabetes mellitus, the insulin-deficient state results in fasting and postprandial hyperaminoacidemia, hyperlipidemia, and hyperglycemia. These metabolic changes and the resulting hyperglycemic milieu can lead to fetal macrosomia that will result in maternal and fetal morbidity. Therefore, normalization of these fuels with the use of intensive insulin regimens is the goal of therapy during pregnancy.
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PMID:Metabolic changes in diabetic and nondiabetic subjects during pregnancy. 813 54

To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat) for 12 weeks. The body weight of mice on the high-fat diet increased significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/- 0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001); corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L, respectively (P < .001). Mice given a high-fat diet also had elevated levels of total cholesterol, triglycerides, and free fatty acids (FFAs) compared with controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected intraperitoneally. The insulinotropic response to glucose was not different between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose-induced insulin secretion was markedly impaired in high-fat diet-treated mice (P < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol-stimulated insulin secretion was potentiated (P < .01), whereas carbachol-stimulated glucagon secretion was not significantly altered. Furthermore, after 12 weeks on the high-fat diet, insulin secretion from isolated islets was impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05). Moreover, islet morphology as examined by immunocytochemistry using insulin antibodies and islet innervation, as revealed by immunostaining of tyrosine hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for 12 weeks. However, quantitative in situ hybridization showed a 3.5-fold upregulation of insulin gene expression in response to the high-fat diet (P < .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude that as little as 1 week of treatment with a high-fat diet induces insulin resistance in C57BL/6J mice. This is accompanied later by hyperlipemia, potentiated carbachol-stimulated insulin secretion, and increased insulin gene expression but impaired glucose-stimulated insulin secretion. We suggest that after several weeks' duration, insulin resistance is accompanied by enhanced islet sensitivity to cholinergic activation and exaggerated insulin gene expression, whereas the failing islet sensitivity to glucose represents decompensation.
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PMID:Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice. 900 77

Glucagon and insulin were measured by heterologous immunoassays in plasma samples of 17 garden warblers (Sylvia borin) kept under constant ad libitum or fasting-refeeding conditions during the migratory season from September to May. Plasma levels of key metabolic indicators (glucose, triglycerides, cholesterol, and free fatty acids) were measured every 2 weeks. Measurements of the two hormones concur with the general assumption of a higher glucagon:insulin ratio, indicating a more pronounced catabolism in birds than in mammals. The concentrations of both hormones varied (insulin: 0.7-7.7 microIU/ml, n = 66; glucagon: 0.4-4.5 ng/ml, n = 99), but differences between mean values per month were significant only for glucagon. Neither hormone titer correlated with either the seasonal or a fasting-refeeding-induced body mass cycle. However, there was a positive correlation between food intake, changes in body mass, and plasma triglycerides and insulin; in contrast, there was a negative relationship with the glucagon:insulin ratio. Glucagon showed only a small negative relationship to plasma glucose and cholesterol, but correlated directly more closely with plasma free fatty acids. The present data support the fact that glucagon is more lypolytic in birds than in mammals. Pancreatic hormones are suggested to participate in the regulation of premigratory hyperphagia and hyperlipemia.
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PMID:A role for pancreatic hormones in the regulation of autumnal fat deposition of the garden warbler (Sylvia borin)? 924 24

Non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes) is a heterogeneous disease resulting from a dynamic interaction between defects in insulin secretion and insulin action. There are various pharmacological approaches to improving glucose homeostasis, but those currently used in clinical practice either do not succeed in restoring normoglycaemia in most patients or fail after a variable period of time. For glycaemic regulation, 4 classes of drugs are currently available: sulphonylureas, biguanides (metformin), alpha-glucosidase inhibitors (acarbose) and insulin, each of which has a different mode and site of action. These standard pharmacological treatments may be used individually for certain types of patients, or may be combined in a stepwise fashion to provide more ideal glycaemic control for most patients. Adjunct treatments comprise a few pharmacological approaches which may help to improve glycaemic control by correcting some abnormalities frequently associated with NIDDM, such as obesity (serotoninergic anorectic agents) and hyperlipidaemia (benfluorex). There is intensive pharmaceutical research to find new drugs able to stimulate insulin secretion (new sulphonylurea or nonsulphonylurea derivatives, glucagon-like peptide-1), improve insulin action (thiazolidinediones, lipid interfering agents, glucagon antagonists, vanadium compounds) or reduce carbohydrate absorption (miglitol, amylin analogues, glucagon-like peptide-1). Further studies should demonstrate the superiority of these new compounds over the standard antidiabetic agents as well as their optimal mode of administration, alone or in combination with currently available drugs.
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PMID:Drug treatment of non-insulin-dependent diabetes mellitus in the 1990s. Achievements and future developments. 927

Several nondigestible but fermentable dietary carbohydrates are able to regulate lipemia and triglyceridemia in both humans and animals. The mechanism of their serum lipid-lowering effect remains to be elucidated. Oligofructose, which is a mixture of nondigestible and fermentable fructans, can decrease triacylglycerol in VLDL when given to rats. The triacylglycerol-lowering action of oligofructose is due to a reduction of de novo fatty acid synthesis in the liver through inhibition of all lipogenic enzymes, namely acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthase, malic enzyme (EC 1.1.1.40), ATP citrate lyase (EC 4.1.3.8), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). Our results suggest that oligofructose decreases lipogenic enzyme gene expression. Postprandial insulin and glucose concentrations are low in the serum of oligofructose-fed animals and this could explain, at least partially, the metabolic effect of oligofructose. Moreover, some events occurring in the gastrointestinal tract after oligofructose feeding could be involved in the antilipogenic effect of this fructan: the production of propionate through fermentation, a modulation of the intestinal production of incretins (namely glucose-dependent insulinotropic peptide and glucagon-like peptide-1), or the modification of the availability of digestible carbohydrates. Recent studies showed that the hypotriglyceridemic effect of fructans also occurs in humans.
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PMID:Effects of fructans-type prebiotics on lipid metabolism. 1115 57

The insulin gene promoter contains many transcriptional response elements that predispose the gene to a wide range of regulatory signals. Glucagon-like peptide 1 (GLP-1) stimulates insulin gene transcription by intracellular second messenger cascades leading to direct transcription factor activation or to the up-regulation of insulin promoter specific transcription factors. In these studies, we have identified a novel regulatory signaling mechanism acting on the rat insulin 1 promoter (rINS1) in the INS-1 beta-cell line. In the presence of stimulatory concentrations of GLP-1 (0.1--100 nM) on rINS1 activity, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) using SB 203580 resulted in a marked increase in promoter activity (maximum 3-fold) over GLP-1 alone, as determined by rINS1 promoter-luciferase reporter gene expression. This effect was revealed to be mediated via the cAMP response element (CRE) of rINS1, because site directed mutagenesis of the CRE motif in rINS1 abolished the increased response to SB 203580. Furthermore, inhibition of p38 MAPK uncovered a similar, more pronounced, response in the expression of a generic CRE promoter driven reporter gene. Time course dose-response studies indicate that the p38 MAPK induced inhibitory response may involve expression of immediate early genes (IEGs); maximum repression of rINS1 activity occurred after 4 h of treatment, comparable with regulatory responses by IEGs. In conclusion, these results demonstrate a novel signaling mechanism whereby p38 MAPK represses rINS1 promoter activity in response to GLP-1, suggesting the involvement of a robust regulatory control by p38 MAPK in insulin gene expression. The relevance of this mechanism may be most apparent during periods of cellular stress in which p38 MAPK activity is stimulated. In this regard, reduced insulin expression levels caused by chronic hyperglycemia (glucotoxicity) and/or hyperlipidemia (lipotoxicity) may be a direct consequence of this mechanism.
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PMID:Insulinotropic hormone glucagon-like peptide 1 (GLP-1) activation of insulin gene promoter inhibited by p38 mitogen-activated protein kinase. 1118 33


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