Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells

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.

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

Biochemical Journal ◽

10.1042/bj2620313 ◽

1989 ◽

Vol 262 (1) ◽

pp. 313-319 ◽

Cited By ~ 14

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.

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Oxidized low-density lipoprotein (LDL) enhances thromboxane A2 synthesis by platelets, but lysolecithin as a product of LDL oxidation has an inhibitory effect

Prostaglandins & Other Lipid Mediators ◽

10.1016/s0090-6980(00)00078-2 ◽

2000 ◽

Vol 62 (2) ◽

pp. 183-200 ◽

Cited By ~ 8

Author(s):

Mohamedain M. Mahfouz ◽

Fred A. Kummerow

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Thromboxane A2 ◽

Inhibitory Effect ◽

Ldl Oxidation ◽

Low Density ◽

Oxidized Low Density Lipoprotein

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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

Biochemical Journal ◽

10.1042/bj3140103 ◽

1996 ◽

Vol 314 (1) ◽

pp. 103-108 ◽

Cited By ~ 2

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.

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