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 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 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.

scholarly journals Regulation of hepatic very-low-density lipoprotein secretion in rats fed on a diet high in unsaturated fat

1987 ◽  
Vol 243 (2) ◽  
pp. 487-492 ◽  
Author(s):  
G F Gibbons ◽  
C R Pullinger
Keyword(s):  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Chow Diet ◽  
Dark Phase ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Unsaturated Fat ◽  
Wide Range ◽  
Cholesterol Secretion

Rats were fed ad libitum on either a standard, high-carbohydrate, chow diet or a similar diet supplemented with 15% unsaturated fat (corn oil). Hepatocytes were prepared either during the dark phase (D6-hepatocytes) or during the light phase (L2-hepatocytes) of the diurnal cycle. In hepatocytes from rats fed on the unsaturated-fat-containing diet, secretion of very-low-density lipoprotein (VLDL) triacylglycerol was inhibited to a greater extent in the D6- than in the L2-hepatocytes. Plasma non-esterified fatty acid concentrations were elevated to the same extent at both D6 and L2 in the unsaturated-fat-fed animals. The secretion of VLDL esterified and non-esterified cholesterol was relatively insensitive to changes in the unsaturated-fat content of the diet. This resulted in proportionate increases in the content of these lipid constituents compared with that of triacylglycerol in the nascent VLDL. There was also an increase in the ratio of esterified to non-esterified cholesterol in the nascent VLDL produced by hepatocytes of the unsaturated-fat-fed animals. In the D6-hepatocytes from the unsaturated-fat-fed animals, the decrease in the secretion of VLDL triacylglycerol could not be reversed by addition of exogenous oleate (0.7 mM) to the incubation medium. In contrast, addition of a mixture of lactate (10 mM) and pyruvate (1 mM) stimulated both fatty acid synthesis de novo and the rate of VLDL triacylglycerol secretion. Secretion of esterified and non-esterified cholesterol also increased under these conditions. Insulin suppressed the secretion of VLDL triacylglycerol and cholesteryl ester under a wide range of conditions in all types of hepatocyte preparations. Non-esterified cholesterol secretion was unaffected. In hepatocytes prepared from the fat-fed animals, these effects of insulin were more pronounced at D6 than at L2. Glucagon also inhibited VLDL lipid secretion in all types of hepatocyte preparations. The decrease in cholesterol secretion was due equally to decreases in the rates of secretion of both esterified and non-esterified cholesterol.

Metabolism of very-low-density lipoprotein and chylomicrons by streptozotocin-induced diabetic rat heart: effects of diabetes and lipoprotein preference

2008 ◽  
Vol 295 (5) ◽  
pp. E1106-E1116 ◽  
Author(s):  
You-Guo Niu ◽  
Rhys D. Evans
Keyword(s):  
Glucose Oxidation ◽  
Early Stage ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
And Control

Very-low-density lipoprotein (VLDL) and chylomicrons (CM) are major sources of fatty acid supply to the heart, but little is known about their metabolism in diabetic myocardium. To investigate this, working hearts isolated from control rats and diabetic rats 2 wk following streptozotocin (STZ) injection were perfused with control and diabetic lipoproteins. Analysis of the diabetic lipoproteins showed that both VLDL and CM were altered compared with control lipoproteins; both were smaller and had different apolipoprotein composition. Heparin-releasable lipoprotein lipase (HR-LPL) activity was increased in STZ-induced diabetic hearts, but tissue residual LPL activity was decreased; moreover, diabetic lipoproteins stimulated HR-LPL activity in both diabetic and control hearts. Diabetic hearts oxidized lipoprotein-triacylglycerol (TAG) to a significantly greater extent than controls (>80% compared with deposition as tissue lipid), and the oxidation rate of exogenous lipoprotein-TAG was increased significantly in diabetic hearts regardless of TAG source. Significantly increased intracardiomyocyte TAG accumulation was found in diabetic hearts, although cardiac mechanical function was not inhibited, suggesting that lipotoxicity precedes impaired cardiac performance. Glucose oxidation was significantly decreased in diabetic hearts; additionally, however, diabetic lipoproteins decreased glucose oxidation in diabetic and control hearts. These results demonstrate increased TAG-rich lipoprotein metabolism concomitant with decreased glucose oxidation in type 1 diabetic hearts, and the alterations in cardiac lipoprotein metabolism may be due to the properties of diabetic TAG-rich lipoproteins as well as the diabetic state of the myocardium. These changes were not related to cardiomyopathy at this early stage of diabetes.

scholarly journals Restoration in vitro of normal rates of very-low-density lipoprotein triacylglycerol and apoprotein B secretion in hepatocyte cultures from diabetic rats

1993 ◽  
Vol 294 (1) ◽  
pp. 167-171 ◽  
Author(s):  
J M Duerden ◽  
G F Gibbons
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Basal Medium ◽  
Inhibitory Response ◽  
Diabetic Rats ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Culture Dish ◽  
Apoprotein B

Hepatocytes derived from diabetic rats were cultured in serum-free Waymouth's medium containing various supplements, after an initial 4 h period during which the cells were allowed to attach to the culture dish in the presence of foetal-bovine serum (10%). After removal of serum, these cells secreted much less very-low-density lipoprotein (VLDL) apoprotein B (apoB) and triacylglycerol than those derived from normal rats when cultured for 24 h in the basal medium. Inclusion of oleate (0.75 mM) in the medium initially increased the output of apoB and triacylglycerol, but the rates remained lower than those observed in normal hepatocytes and declined to zero after 72 h. This time-dependent decline in VLDL output was prevented by addition of dexamethasone to the oleate-containing medium. Levels of apoB and triacylglycerol output characteristic of normal hepatocytes could only be completely restored, however, by further addition of a mixture of lipogenic substrates (lactate plus pyruvate) to the medium. Restoration of normal levels of VLDL secretion in diabetic hepatocytes in vitro by this means was accompanied by a normal inhibitory response of apoB and triacylglycerol output to short-term (24 h) treatment with insulin or glucagon. Exposure of the cells to insulin for 72 h enhanced the secretion of VLDL, whereas treatment with glucagon for the same period potentiated the original inhibitory effect. The defective secretion of VLDL apoB observed when diabetic hepatocytes were cultured in the basal medium for 24 h could also be rectified by inclusion of a mixture of oleate (0.75 mM), lactate (10 mM), pyruvate (1 mM), dexamethasone (1 microM) and insulin (78 nM) in the medium during the 4 h attachment period in the presence of serum. Under these conditions, the increase in the secretory response of triacylglycerol was not so pronounced.

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.

Beneficial role of Taurine on Biochemical Parameters of Diabetic Female Rats

2019 ◽  
Vol 10 (04) ◽  
pp. 662-666
Author(s):  
Alyaa Majid ◽  
Mohannad A Gata ◽  
Khalid G Al-Fartosi ◽  
Sarah S Sayer
Keyword(s):  
Oxidative Stress ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Female Rats ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Taurine Supplementation ◽  
Positive Effects

For studying the positive effects of taurine (TAU) on lipid and glucose metabolism. Moreover, the present paper examines the positive roles of glucose and lipid on the correction of oxidative stress diabetes-related complications in alloxan diabetic rats. To acheive the objective of study, 24 of female rats ((Rattus norvegicus) have been used. The division of animals was done in 4 groups (6 each). Diabetes was enhanced by injected intraperitoneally with alloxan at a single dose in body weight; 125 mg/kg. Diabetic rats go through a specific rise (P ≤ 0.05) in the glucose levels, triglyceride, total cholesterol, very-low-density lipoprotein, low-density lipoprotein, and malondialdehyde and an important noticeable decrease in high-density lipoprotein, glutathione, and albumin. In addition, taurine supplementation caused a significant reduction in the glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein levels. The obtained results revealed that taurine exhibited an inhibitory effect on oxidative stress indices (MDA) and improved antioxidant levels. Taurine could have potential as a pharmaceutical drug for diabetes mellitus (DM), and this invites further studies in this field.

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