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

Examination of glucose kinetics, pancreatic alpha and beta cell function, plasma lipids, urinary acidification and calcium excretion has been undertaken in a patient with hereditary fructose intolerance. This case was unusual as it was associated with insulin-requiring diabetes, type IV hyperlipemia, hypercalciuria and renal calculi. He also demonstrated the previously described fructose-induced defect of urine acidification. Glucagon and C-peptide assays showed that the pancreatic alpha cells were stimulated by fructose and that the beta cells did not respond to fructose. It is not known whether the latter was due to his diabetes or to the lack of a beta cell response to this sugar. Primed 14C-glucose infusions were used for the first time to study nonsteady state glucose kinetics in man. They showed that, 24 hours after the last insulin injection and under basal conditions, the glucose concentrations increased because glucose production exceeded glucose utilization. However, after the administration of sorbitol the plasma glucose concentration decreased because glucose production decreased. After the administration of sorbitol there was no change in the metabolic clearance of glucose. This reflects the lack of a peripheral insulin effect and is consistent with the lack of any measurable C-peptide. Glucose utilization also decreased, but this decrease was less than the decrease in glucose production. Because the metabolic clearance of glucose remained unchanged, it was concluded that the change in glucose utilization was solely due to the decrease in glucose concentration. The absence of C-peptide in the plasma indicated that changes in glucose turnover were not related to any changes in endogenous plasma insulin. Furthermore, the plasma glucagon concentration increased and, hence, changes in this hormone could not account for the decrease in glucose production. Therefore, it was concluded that the sorbitol-induced decline in glucose production was due to a direct effect on hepatic metabolism.
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PMID:Studies of glucose turnover and renal function in an unusual case of hereditary fructose intolerance. 1 54

After enteral administration of 200 mg/kg alpha-hexachlorocyclohexane (alpha-HCH) female Wistar rats develop a hyperlipemia. 48 h after administration of alpha-HCH, serum triglycerides are increased by 300%, whereas both serum cholesterol and serum total phospholipids only increase by about 45%. Serum free fatty acids are not significantly altered. Fractionation of the serum lipoproteins by ultracentrifugation shows that the hyperlipemia is due to a fivefold increase in serum very low density lipoproteins. Hepatic triglyceride secretion, calculated after i.v. injection of Triton WR 1339, is increased in animals pretreated wtih alpha-HCH. Corresponding to this observation, drugs known to diminish the triglyceride secretion of the liver, such as actinomycin D, cycloheximide; glucagon, orotic acid, CFT 1201, and CFT 1042 reduce the alpha-HCH-induced hyperlipemia. We concluded from the results that hyperlipoproteinemia after alpha-HCH is due to an increased hepatic very low density lipoprotein secretion. At the same time, the blood sugar level was decreased in fasting animals after treatment with alpha-HCH. Earlier experiments suggest that this effect is due to a decreased gluconeogenesis in the liver.
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PMID:Increase of serum very low density lipoproteins in rats after administration of alpha-hexachlorocyclohexane. 6 95

This paper reviews most of the clinical studies on the mode of action of halofenate, an established hypolipidemichypouricemic agent in man. In yeast cutlures and in isolated rat adipocytes, halofenate was found to inhibit the conversion of pyruvate to acetyl CoA. While pyruvate dehydrogenase was inhibited in vitro, halofenate also inhibited the activety of various other isolated enzymes. In rats maintained on halofenate in the diet (0.02-0.10%) for 2-14 days, there were 20-40% decreases in plasma cholesterol, trigly cerides, phospholipids, and free fatty acids. Inhibition of liver HMG-CoTA reductase does not appear to account for the hypocholesterolemic effect, and activation of mitochondrial alpha-glycerophosphate dehydrogenase does not explain the hypotriglyceridemic action. Kinetic measurements of the serum appearance and disappearance of triglycerides in drug-treated rats suggest that the hypotriglyceridemic activity is due to a net inhibition of hepatic triglyceride synthesis. Reduction of very low density lipoprotein (VLDL) and high density lipoprotein (HDL) levels in rats with sucrose-induced hyperlipidemia and normalization of the altered apolipoprotein profiles are in accord with the effects of halofenate on plasma triglyceride and cholesterol levels. The reduced insulin-to-glucagon ratio observed in Zucker obese hyperlipemic rats is also consistent with halofenat's hypotriglyceridemic activity. Preliminary experiments in rats on the mechanism of its hypoglycemic activity, observed in some diabetic hyperlipidemic patients, indicate that halofenate acts differently than conventional oral hypoglycemic agents. Some, but not all, of the effects of halofenate were observed with clofibrate at two to ten times higher levels.
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PMID:Studies on the mechanism of action of halofenate. 31 18

Obesity in the Zucker rat is accompanied by hyperlipemia, hyperinsulinism, insulin resistance, pancreatic hyperplasia, and islet hypertrophy. This study correlates the morphologic heterogeneity of isolated pancreatic islets with secretion of insulin and glucagon in the perifusion system. Islet size was arbitrarily defined as large (greater than 0.45 mm) or small (smaller than 0.12 mm). Protein content and volume (V = 4/3pir3) were calculated for groups and individual islets, respectively. Islets from obese rats secreted more insulin in response to glucose and aminophylline than islets from lean rats (peak 7.8 +/- 2.4 vs. 1.5 +/- 0.37 microU/islet/min, P less than 0.005). Insulin release was related directly to islet size and protein content. Small islets from lean and obese animals produced less insulin per islet than large islets (P less than 0.005). In terms of islet volume, however, large islets were inefficient insulin releasers as compared to small islets (P less than 0.005). Stimulation with Br-cAMP released glucagon from islets of lean but not from large islets of obese animals (peak 11 +/- 3.3 vs. 4.1 +/- 0.3 pg/microgram protein per minute, P less than 0.05). Arginine produced the same effect on glucagon release (P less than 0.05) as stimulation with Br-cAMP. The observed increased insulin release rates and the blunted glucagon response are related to islet size in the pancreas of the Zucker rat.
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PMID:Correlation between morphology and function in isolated islets of the Zucker rat. 37 79

Chronic exercise training is recognized to reduce plasma lipid levels in man and animals, but the mechanism(s) mediating this phenomenon have not been defined. In the present study, we examined triglyceride (TG) production and disposal in vivo in a genetic model of human type IV hyperlipemia, the obese Zucker rat. Utilizing the normolipemic thin littermate as the control, we investigated endogenous production of TG utilizing the Triton methodology and peripheral disposal of an exogenous lipid emulsion utilizing Intralipid injection. In the sedentary state, the hyperlipemic obese Zucker rat demonstrated a threefold elevation in triglyceride secretion rate relative to the normolipemic thin littermate. After a 3-wk period of exercise training, a reduction of basal plasma TG concentration of 42% was associated with a 51% reduction in TG secretion rate, a change adequate to account for the hypolipemic response. Moreover, chronic exercise training also improved the ability to dispose of an Intralipid load. A similar reduction in TG production with reduced TG removal was observed in the thin normolipemic rats, a result that suggests that the lipid lowering response to exercise training may be predominantly mediated by reduced secretion of TG. The possible relationship between reduced TG secretion and alterations in the bihormonal axis of insulin and glucagon are discussed.
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PMID:Reduced triglyceride secretion: a metabolic consequence of chronic exercise. 62 36

Significant hypertriglyceridemia, the most common lipid abnormality in renal failure, first occurs when the creatinine clearance falls to 50 ml/min. The prevalence of hypertriglyceridemia continues to rise as creatinine clearance falls further with the highest rate developing at a creatinine clearance less than 10 ml/min. Hypertriglyceridemia is correlated with plasma glucagon levels but not growth hormone or insulin. Plasma cholesterol values remain normal in the face of deteriorating renal function and show no correlation with any of the hormones measured. Although all three hormones became elevated as renal function diminished, none were directly correlated with glomerular filtration rate. There was a distinct decrease in the prevalence of hyperlipidemia after 5 years of maintenance hemodialysis therapy. Plasma growth hormone and glucagon through an effect on plasma triglyceride and plasma insulin by effecting plasma cholesterol may play a role in this decline of hyperlipidemia with duration of hemodialysis.
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PMID:Relationship of plasma lipids to renal function and length of time on maintenance hemodialysis. 70 43

The effect of medroxyprogesterone acetate (MPA) on basal circulating lipids, arginine-stimulated glucagon and insulin secretion, and glucose tolerance was studied in normal women. After 5 days of oral MPA treatment (10 mg/day), there was a small but significant decline in basal circulating triglycerides. No changes were observed in fasting plasma concentrations of cholesterol, free fatty acids, glucagon, insulin, or glucose; in the plasma glucagon, insulin, or glucose responses during L-arginine infusion; or in the plasma insulin or glucose responses during oral glucose tolerance tests. There was no correlation of any of these parameters with the observed decline in fasting plasma triglyceride concentrations. These results confirm previous reports of no consistent changes in lipid or glucose homeostasis in women using derivatives of 17alpha-acetoxyprogesterone derivatives for contraceptive purposes, and suggest that MPA may be a suitable alternative for those women who develop hyperlipemia or glucose intolerance when they use contraceptive agents which contain derivatives of ethinyl estradiol and nortestosterone.
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PMID:Effect of contraceptive steroids on arginine-stimulated glucagon and insulin secretion in women. III. Medroxyprogesterone acetate. 90 95

Our study indicates that in renal failure elevated plasma triglyceride can first be detected when the GFR falls to 50 ml/min. Hypertriglyceridemia is the commonest abnormality found and increases further when the GFR falls below 10 ml/min. Plasma cholesterol levels remain normal even at low levels of renal function. Although plasma growth hormone, glucagon, and insulin levels become elevated when renal function diminishes, there is no definite correlation of their levels and GFR. A decreased incidence of hyperlipidemia observed in patients sustained by maintenance hemodialysis for over 5 yrs may in part be due to the triglyceride lowering effect of growth hormone and glucagon and/or the cholesterol lowering effect of insulin.
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PMID:Uremic hyperlipoproteinemia: correlation with residual renal function and duration of maintenance hemodialysis. 91 Mar 86

The effects of acute and chronic differences in the carbohydrate content of the diet on plasma insulin, glucagon, insulin-glucagon molar ratio (I/G), and triglycerides were studied. Acute effects were studied by varying the carbohydrate content of a single test meal, while chronic effects were determined by varying the carbohydrate content of the diet for a week. A test meal containing 0.6 gm of gelatin per kilogram plus 0.6 gm. per kilogram of glucose resulted in much higher levels of insulin and I/G (p smaller than 0.005), lower glucagon levels (p smaller than 0.05), and slightly higher triglycerides (N.S.) than did a meal of 1.2 gm, per kilogram of gelatin alone. One week of a 12 gm. carbohydrate, 2870-calorie diet lowered insulin (p smaller than 0.001), I/G (p smaller than 0.05), and triglycerides (p smaller than 0.001) and increased glucagon (N.S.), whereas a 390-gm. carbohydrate, 2784-calorie intake significantly increased insulin, I/G, and triglycerides (p smaller than 0.005) and lowered glucagon (p smaller than 0.02) within two days; even greater changes in hormones were observed on a 510-gm. carbohydrate intake. Of those patients in whom a high carbohydrate intake induced a triglyceride rise of at least 40 mg. per deciliter, a significant correlation between the change in I/G and the change in triglycerides was noted (r equals 0.85; p smaller than 0.01). The results are compatible with but do not prove the proposal that pancreatic alpha and beta cells play a mediating role in carbohydrate induction of hyperlipidemia.
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PMID:Basal and postprotein insulin and glucagon levels during a high and low carbohydrate intake and their relationships to plasma triglycerides. 109 39

Transient lowering of blood levels of free fatty acids (FFA) in man and experimental animals after ingestion of fat has been noted by many investigators and has been attributed to inhibition of mobilization of fatty acids from adipose tissue. Studies on lipid mobilizing activity in in vitro systems containing glucagon, insulin and anti-insulin anti-bodies as factors modifying lipolysis indicate that insulin is the basic inhibitor of lipolysis in the blood in the period immediately following feeding of animals. This observation has been confirmed by direct determinations of insulin levels by the radioimmunologic method. Experiments in which substances influencing activity of the autonomic nervous system were used show that ingestion of fats stimulates insulin secretion as a result of cholinergic stimulation. Studies on lipolytic activity of blood serum confirmed an essential role of lipoprotein lipase in the mechanism of deposition of triglycerides in adipose tissue during alimentary lipemia. The role of prostaglandins and intestinal hormones (enteroinsular axis) in the mechanism of regulation of FFA levels during alimentary lipemia is also discussed.
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PMID:Factors regulating blood levels of free fatty acids during alimentary lipemia. 118 13


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