scholarly journals Decreased sensitivity of very-low-density lipoprotein secretion to the inhibitory effect of insulin in cultured hepatocytes from lactating rats

1996 ◽  
Vol 316 (3) ◽  
pp. 737-741 ◽  
Author(s):  
Catherine S. BOURGEOIS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Milk Fat ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Defined Medium ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Inhibitory Effects ◽  
Insulin Resistant ◽  
Lactating Mammary Gland

Hepatocytes were prepared from 10–11-day lactating rat dams and from lactating dams which had been weaned for periods of either 1–2 days or 7 days. Hepatocytes from each group were cultured for periods of up to 48 h in a chemically defined medium. Compared with those from the 7-day weaned animals, hepatocytes from the lactating rats were resistant to the inhibitory effects of insulin on the secretion of very-low-density lipoprotein (VLDL) triacylglycerol (TAG). These differences persisted for up to 48 h in culture. Hepatocytes from the 1–2-day weaned animals remained relatively insulin-resistant in this respect. Similar differences in the response to insulin were not observed for the secretion of VLDL apolipoprotein B. TAG production increased and ketogenesis decreased in the hepatocytes from the lactating compared with those from the 7-day weaned rats. Insensitivity of the liver to the normal effects of insulin on the secretion of VLDL TAG may arise from a need to maintain an adequate flux of hepatic lipids to the lactating mammary gland in order to meet the large demand for milk-fat production.

scholarly journals Regulation of very-low-density-lipoprotein lipid secretion in hepatocyte cultures derived from diabetic animals

1989 ◽  
Vol 262 (1) ◽  
pp. 313-319 ◽  
Author(s):  
J M Duerden ◽  
S M Bartlett ◽  
G F Gibbons
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Whole Body ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Short Period ◽  
Streptozotocin Diabetic Rats ◽  
Cholesterol Secretion

Hepatocytes were derived from 2-3-day streptozotocin-diabetic rats and maintained in culture for up to 3 days. Compared with similar cultures from normal animals, these hepatocytes secreted less very-low-density-lipoprotein (VLDL) triacylglycerol, but the decrease in the secretion of VLDL non-esterified and esterified cholesterol was not so pronounced. This resulted in the secretion of relatively cholesterol-rich VLDL particles by the diabetic hepatocytes. Addition of insulin for a relatively short period (24 h) further decreased the low rates of VLDL triacylglycerol secretion from the diabetic hepatocytes. The secretion of VLDL esterified and non-esterified cholesterol also declined. These changes occurred irrespective of whether or not exogenous fatty acids were present in the culture medium. Little or no inhibitory effect of insulin was observed after longer-term (24-48 h) exposure to the hormone. Both dexamethasone and a mixture of lipogenic precursors (lactate plus pyruvate) stimulated VLDL triacylglycerol and cholesterol secretion, but not to the levels observed in hepatocytes from normal animals. The low rate of hepatic VLDL secretion in diabetes contrasts with the increase in whole-body VLDL production rate. This suggests that the intestine is a major source of plasma VLDL in insulin-deficient diabetes.

scholarly journals Chronic exogenous hyperinsulinaemia does not modify the acute inhibitory effect of insulin on the secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B in primary cultures of rat hepatocytes

1996 ◽  
Vol 314 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Catherine S. BOURGEOIS ◽  
David WIGGINS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Primary Cultures ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Cell Protein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Plasma Insulin Concentration

Male Wistar rats were fitted with subcutaneous osmotic minipumps that delivered insulin at a constant rate of 0.20 i.u./h for 7 days. This treatment raised the plasma insulin concentration from 31±4 to 201±64 μ-i.u./ml. Hepatocytes prepared from the hyperinsulinaemic animals secreted very-low-density lipoprotein (VLDL) triacylglycerol (TAG) at a higher rate (172±21 μg per 24 h per mg cell protein) than did those from sham-operated controls (109±12 μg per 24 h per mg) (P < 0.05). However, chronic exogenous hyperinsulinaemia had no stimulatory effect on the secretion of VLDL apolipoprotein B (apoB) in derived hepatocytes compared with those from the sham-operated controls (2.32±0.38 compared with 3.09±0.40 μg per 24 h per mg). Hepatocytes from the hyperinsulinaemic rats thus secreted larger VLDL particles as evidenced by the increased TAG:apoB ratio (78.4±13.1 compared with 38.4±7.6; P < 0.05). In hepatocytes from the hyperinsulinaemic rats a larger proportion of the newly synthesized TAG was secreted as VLDL. Hepatocytes from the hyperinsulinaemic and the sham-operated control animals were equally sensitive to the inhibitory effect of insulin added in vitro on the secretion of VLDL TAG. Insulin added in vitro to the culture medium of hepatocytes from hyperinsulinaemic animals significantly decreased the TAG:apoB ratio of the secreted VLDL. This change did not occur in hepatocytes from sham-operated rats. These results suggest that, in vivo, chronic hyperinsulinaemia is not in itself sufficient to desensitize the liver to the acute inhibitory effect of insulin on the secretion of VLDL.

Very Low Density Lipoprotein Overproduction Is Maximally Expressed in Early Insulin Resistant States

1999 ◽  
Vol 892 (1 THE METABOLIC) ◽  
pp. 319-322 ◽  
Author(s):  
JENS PIETZSCH ◽  
ULRICH JULIUS ◽  
CHRISTIAN KIRCH ◽  
SABINE FISCHER ◽  
MARKOLF HANEFELD
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Insulin Resistant

scholarly journals Decreased secretion of very-low-density lipoprotein triacylglycerol and apolipoprotein B is associated with decreased intracellular triacylglycerol lipolysis in hepatocytes derived from rats fed orotic acid or n–3 fatty acids

1997 ◽  
Vol 325 (3) ◽  
pp. 711-719 ◽  
Author(s):  
Abdel-Malek HEBBACHI ◽  
Marilia C. L. SEELAENDER ◽  
Paul W. BAKER ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Apolipoprotein B ◽  
Orotic Acid ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Chow Diet ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apob Secretion

Hepatocytes from rats fed a chow (control) diet or from rats fed a chow diet supplemented with either orotic acid (OA; 1%, w/w) or fish oil (FO; 20%, v/w) were maintained in culture for periods up to 48 h. During the first 24 h period, the low rates of output of very-low-density lipoprotein (VLDL)-associated triacylglycerol (TAG) and apolipoprotein B (apoB) in hepatocytes from the FO- and OA-fed animals were associated with significantly lower rates of intracellular TAG lipolysis and re-esterification. Most of the VLDL TAG secreted was mobilized via lipolysis of the intracellular TAG pool, but the proportion of VLDL TAG secreted via this route in cells from the FO-fed and OA-fed animals was decreased compared with that in the control-fed animals' cells. In the presence of exogenous oleate the inhibitory effect of OA feeding on VLDL apoB and TAG secretion persisted in the derived hepatocytes for up to 48 h following isolation. However, when oleate was absent no inhibitory effect on the secretion of TAG and apoB was observed between 24 and 48 h. Under these conditions the rate of intracellular TAG turnover returned to normal. The initial inhibitory effect of FO feeding on VLDL TAG and apoB secretion did not persist in the derived hepatocytes between 24 h and 48 h of culture in the presence of exogenous oleate. Although intracellular TAG lipolysis and VLDL TAG and apoB secretion rates appear to be positively correlated, a causal relationship has not been conclusively established.

Prevention of myocardial disease in JCR:LA-corpulent rats by running

1989 ◽  
Vol 66 (4) ◽  
pp. 1649-1655 ◽  
Author(s):  
J. C. Russell ◽  
R. M. Amy ◽  
V. Manickavel ◽  
P. J. Dolphin ◽  
W. F. Epling ◽  
...  
Keyword(s):  
Food Restriction ◽  
Low Density Lipoprotein ◽  
Disease Process ◽  
Density Lipoprotein ◽  
Male Rats ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Cell Hyperplasia ◽  
Significant Drop ◽  
Insulin Resistant

The JCR:LA-corpulent rat is a congenic strain that, if homozygous for the cp gene, is obese with a very low-density lipoprotein hyperlipidemia and is insulin resistant. The male corpulent rats develop atherosclerotic lesions of the major arteries and myocardial lesions. Corpulent and lean male rats were induced through mild food restriction to run intensively (approximately 6,000 m/day) from 6 wk to 6 mo of age. Food restriction, especially when coupled with running, lowered all classes of lipids in the whole serum of corpulent rats. The principal changes in lipid concentrations were in the very low-density lipoprotein fraction. Food restriction caused a significant drop in fasting insulin levels of corpulent rats and decreased beta-cell hyperplasia. Both effects were more marked in the running animals. There was a significant decrease in myocardial lesion frequency in the food-restricted corpulent rats and an absence of lesions in the running rats. The results indicate that intensive physical activity can largely correct the lipid abnormalities and insulin resistance of this atherosclerosis-prone strain, and these changes are associated with inhibition of the disease process. However, moderate food restriction has similar effects, and the greater effects seen with intensive running may simply reflect an effectively more severe metabolic restriction in the presence of the exercise.

Studies on the Thromboplastic Effect of Human Plasma Lipoproteins

1976 ◽  
Vol 35 (01) ◽  
pp. 178-185 ◽  
Author(s):  
Helena Sandberg ◽  
Lars-Olov Andersson
Keyword(s):  
High Density Lipoprotein ◽  
Human Plasma ◽  
Platelet Rich Plasma ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Plasma Lipoproteins ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Free Plasma ◽  
Good Agreement

SummaryHuman plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addition of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma.Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.

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