Effect of acute uremia on triglyceride kinetics in the rat

Gregg, Richard C.; Mondon, Carl E.; Reaven, Eve; Reaven, Gerald M.

doi:10.1016/0026-0495(76)90108-6

Cited by 24 publications

(7 citation statements)

References 28 publications

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“…This approach has been described and validated in a previous publication (6). In brief, rats on the standard or hyperlipidemic diets were injected with plasma containing VLDL-TG which had been prelabeled in vivo with Jail]glycerol.…”

Section: Studiesmentioning

confidence: 99%

Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

Reaven¹,

Reaven²

1978

The Journal of Cell Biology

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The fact that colchicine inhibits hepatic secretion of very low density lipoprotein (VLDL) particles has been interpreted to mean that microtubules are involved in hepatic VLDL secretion. To further define this relationship, we have attempted to see if changes in hepatic VLDL secretion are associated with changes in hepatocyte microtubule or tubulin content. Accordingly, hepatic secretion of VLDL was increased in rats, and the hepatocyte content of both microtubules (using quantitative morphometric methods) and tubulin (using a time-decay colchicine binding assay) was determined. In acute experiments, VLDL secretion was increased by perfusion of isolated rat livers for 2 h with varying concentrations of free fatty acids (FFA). Results indicate that hepatic VLDL triglyceride (TG) secretion at perfusate FFA levels of 0.7 /zEq/ml is threefold greater (P < 0.01) than when livers are perfused without added FFA. However, no differences are observed in the content of microtubules in these livers: specifically, microtubules occupy 0.029% of hepatocyte cytoplasm in livers perfused without FFA and 0.030% of cytoplasm in livers perfused with FFA. In chronic experiments, rats were fed for 1 wk with either standard rat chow or a hyperlipidemic (sucrose/ lard) diet. With the experimental diet, plasma triglyceride levels increase threefold over controls, and liver VLDL-TG production, as determined by [3H]glycerol turnover studies, is 55% greater (P < 0.01) than controls. However, microtubules occupy 0.027% of the cytoplasm of hepatocyte cytoplasm whether rats are on standard or hyperlipidemic diets. Furthermore, the tubulin content of isolated hepatocytes does change, and represents 1% of hepatocyte soluble protein, irrespective of diet. These results suggest that increases in hepatic VLDL secretion can occur without any demonstrable change in hepatocyte assembled microtubule or tubulin content, and raise questions as to the role played by microtubules in hepatic VLDL secretion.KEY WORDS microtubule -tubulin hepatocytes very low density lipoprotein secretion hypertriglyceridemia Very low density lipoproteins (VLDL) are important secretory products of the liver (4,7,8,18).Although the pathway of synthesis, intracellular transport and secretion of these particles has been well defined, the factors regulating their intracellular translocation and secretion are still largely unknown. However, circumstantial evidence has led to the suggestion that microtubules are in-J. CELL BIOLOGY 9 The Rockefeller University Press 9 0021-9525/78/0601-073551.00 735on May 12, 2018 jcb.rupress.org Downloaded from

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Section: Studiesmentioning

confidence: 99%

Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

Reaven¹,

Reaven²

1978

The Journal of Cell Biology

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“…Thirty percent of the patients with renal failure have hypertriglyceridemia [69]. Most data suggest that decreased lipolysis of triglyceride-rich lipoproteins is the principal mechanism which causes increments of triglycerides in the plasma [69, 70, 71, 72]. The role of this lipid’s contribution to coronary heart disease in chronic renal failure is conjectural [69].…”

Section: Renal Pathophysiologymentioning

confidence: 99%

Chronic Renal Failure: An Overview from a Pediatric Perspective

Saborío

Hahn²,

Hisano³

et al. 1998

Nephron

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“…The peffusate also contained porcine insulin which was infused at rates of 10 mU/h for young rats and 13 mU/h for old rats in order to maintain perfusate insulin concentration at approximately 50 g/ml. In addition, each liver received continuous infusion (2.3 ml/h) of oleic acid complexed with rat serum solution prepared as previously described [21]. Three different NEFA concentrations (18,36 or 72 mmol/l) were infused in order to attain NrEFA concentrations of approximately 0.4, 0.8 and 1.9 mmol/1.…”

Section: Hepatic Tg Secretionmentioning

confidence: 99%

“…Hepatic TG secretion by livers from control and diabetic rats was determined by in situ peffusion techniques previously described [19][20][21]. All studies were started in the early afternoon, 6 h after food withdrawal.…”

Section: Hepatic Tg Secretionmentioning

confidence: 99%

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Evidence for multiple causality in the development of diabetic hypertriglyceridaemia

1980

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Summary. The relationship between varying degreesof insulin deficiency and hypertriglyceridaemia in rats have been examined. Rats were studied 7-10 days after injection with streptozotocin, and plasma glucose concentrations used to classify rats as having either moderate (200-350 mg/dl) or severe diabetes (> 350 mg/dl). A 2-to 3-fold rise in plasma triglyceride (TG) concentration developed in six week old insulin deficient rats associated with elevated plasma non esterified fatty acid (NEFA) concentrations and decreased very low density lipoprotein secretion. Perfused livers from six week old rats with either moderate or severe diabetes were incapable of increasing hepatic TG secretion when perfusate NEFA concentrations were raised from 0.4 to 1.8 mmol/1. In one year old, spontaneously obese rats, an equivalent degree of hypertriglyceridaemia could be produced with a lesser degree of insulin deficiency, and in this instance very low density lipoprotein secretion was increased over control values. Hepatic TG secretion by perfused livers from these rats with moderate diabetes approximately doubled when perfusate NEFA concentration was raised from 0.40 to 0.85mmol/1. These results emphasize the complex causality of diabetic hypertriglyeridaemia in situations characterised by comparable degrees of fasting hyperglycaemia.Key words: Diabetes, insulin deficiency, hypertriglyceridaemia, very low density liporotein, hepatic peffusion, triglycerides.Albrink has characterised hypertriglyceridaemia as "the hyperlipemia par excellence of the diabetic" [ 1]. There is, however, considerable disagreement concerning the pathogenesis of hypertriglyceridaemia in patients with diabetes. The controversy is particularly applicable to patients with significant fasting hyperglycaemia. Early suggestions were that hypertriglyceridaemia in this situation was due to a defect in lipoprotein removal from the plasma [2-4], presumably secondary to a decrease in lipoprotein lipase (LPL) activity [2][3][4][5][6]. This hypothesis has received support from studies of the effect of chronic insulin deficiency on triglyceride (TG) metabolism in the rat [7][8][9][10] and the dog [11], in which hypertriglyceridaemia was associated with either a decrease in LPL activity [7,8], or the rate of entry of very low density lipoprotein (VLDL)-TG into plasma [9][10][11].Recent measurements of VLDL-TG kinetics in diabetic man are in contrast to these findings, and VLDL-TG secretion rates have been found to be elevated in the majority of adult onset diabetics with significant fasting hyperglycaemia [1,14]. Thus, direct measurements suggest that VLDL-TG secretion is increased, not decreased, in diabetic patients with significant fasting hyperglycaemia. The current experiments were undertaken in an effort to explore some of the reasons for the discrepancies and to see if these apparently dichotomous positions as to the cause of diabetic hypertriglyceridaemia in subjects with significant fasting hyperglycaemia could be reconciled. Methods AnimalsAll experiments were...

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Effect of acute uremia on triglyceride kinetics in the rat

Cited by 24 publications

References 28 publications

Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content

Chronic Renal Failure: An Overview from a Pediatric Perspective

Evidence for multiple causality in the development of diabetic hypertriglyceridaemia

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