The Effect of Diabetes Mellitus on Sterol Synthesis in the Intact Rat

Feingold, Kenneth R.; Wiley, Millie Hughes; MacRae, Gordon; Moser, Arthur H.; Lear, Steven R.; Siperstein, Marvin D.

doi:10.2337/diab.31.5.388

Cited by 50 publications

(13 citation statements)

References 7 publications

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“…Over 6 h, a large fraction of the sterols synthesized in the liver is transported to peripheral tissues. This explains the apparently low contribution of the liver to total-body sterol synthesis reported by Feingold et al (26). Our data from control rats are very similar to those of Jeske and Dietschy (27) and Lakshmanan and Veech (28), who killed their animals 1 and 2 h, respectively, after injection of 3 H 2 O.…”

Section: Discussionsupporting

confidence: 90%

“…Our in vivo data on sterol synthesis in diabetic rats (Table 3) are similar to those of Young et al (25) but are very different from those of Feingold et al (26), who reported that the rate of cholesterol synthesis is unchanged in the liver and increased by 26% in the total body of diabetic compared with control rats. The contribution of the liver to total cholesterol synthesis was 29 and 24% in control and diabetic rats, respectively.…”

Section: Discussionsupporting

confidence: 77%

“…These differences can in part be ascribed to differences in experimental protocol. The rats used by Feingold et al (26) were mildly diabetic because they received a small dose of STZ (40 mg/kg vs. the common dose of 80 mg/kg we used), and ketotic animals were excluded from their study. In addition, rats were killed 6 h after injection of 3 H 2 O (vs. 1 h in our study).…”

Section: Discussionmentioning

confidence: 99%

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Lipogenesis From Ketone Bodies in Perfused Livers From Streptozocin-Induced Diabetic Rats

et al. 1988

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Production of ketone bodies and their contribution to lipogenesis were measured in isolated livers from normal and streptozocin-induced diabetic (STZ-D) rats perfused with tracer amounts of 3H2O and (R)-3-hydroxy[3-14C]butyrate. Diabetes decreased by 80-95% the total rates of fatty acid and 3-beta-hydroxysterol synthesis in perfused livers and livers of live rats. The activity of cytosolic acetoacetyl-CoA synthetase was slightly (17%) decreased in livers from STZ-D rats. The incorporation of ketone bodies into fatty acids and sterols was markedly inhibited in perfused livers from STZ-D rats despite the stimulation of ketogenesis by diabetes and the presence of oleate. Treatment of the rats with insulin before liver perfusion led to a normalization of the rates of ketogenesis and fatty acid synthesis. The rates of sterol synthesis were only partially normalized by insulin treatment. We conclude that in STZ-D, ketosis does not stimulate hepatic lipogenesis via cytosolic activation of acetoacetate.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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Lipogenesis From Ketone Bodies in Perfused Livers From Streptozocin-Induced Diabetic Rats

et al. 1988

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“…The inability of the diabetic rat jejunal EMM to cope with an increased dietary load of cholesterol may be related to the known changes in cholesterol metabolism that are observed in diabetes. Intestinal de novo synthesis of cholesterol has been shown to be increased 2-3-fold in streptozotocin-diabetic rats (40) associated with an increase in 3-hydroxy-3-methylglutaryl-CoA reductase activity (41)(42)(43). Cholesterol feeding did not alter cholesterol synthesis in control animals, but markedly inhibited cholesterol synthesis in the diabetic small intestine (44).…”

Section: Discussionmentioning

confidence: 99%

Dietary ω3 fatty acids and cholesterol modify enterocyte microsomal membrane phospholipids, cholesterol content and phospholipid enzyme activities in diabetic rats

Keelan¹,

Doring²,

Tavernini³

et al. 1994

Lipids

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Diabetes-associated changes in intestinal uptake of nutrients are modified by isocaloric variations in the type of dietary lipids, and are associated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. The present study was designed to test the hypothesis that diet- and diabetes-associated changes in enterocyte microsomal membrane phospholipids are due to variations in the activity of two phospholipid metabolizing enzymes, 1,2-diacylglycerol:CDPcholine cholinephosphotransferase (CPT) and phosphatidylethanolamine methyltransferase (PEMT). Adult female Wistar rats were fed one of four semisynthetic diets--beef tallow low in cholesterol (BT), beef tallow high in cholesterol (BTC), fish oil low in cholesterol (FO) or fish oil high in cholesterol. In half of the animals, diabetes mellitus was produced by injection of streptozotocin. Jejunal and ileal enterocyte microsomes (EMM) were isolated and analyzed for cholesterol and phospholipids, as well as for CPT and PEMT activities. In control animals, feeding FO reduced EMM total phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol. Feeding FO resulted in a greater than 95% reduction in the activity of CPT. Diabetes was associated with increased jejunal EMM total phospholipids including sphingomyelin (SM) and PE, without associated changes in CPT or PEMT. Dietary cholesterol supplementation did not affect EMM total cholesterol or phosphlipid composition in control rats fed BT or FO, but was associated with an increase in EMM cholesterol in diabetic rats fed BT or FO. A decrease in total phospholipids due to a decline in SM, PC and PE in diabetic rats fed FO was not associated with changes in the activities of CPT or PEMT in EMM.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Serum cholesterol and HDL-cholesterol concentrations were increased in these insulin overtreated animals, perhaps as a result of increased food intake. Gut cholesterol synthesis is increased in insulinopenic streptozotocin diabetic rats, and might be expected to be normal or reduced in our over-treated animals [26].…”

Section: Discussionmentioning

confidence: 85%

Very low density lipoprotein metabolism after insulin over‐treatment and during a euglycaemic clamp

Kruszynska

Home

Alberti

1987

Eur J Clin Investigation

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The disturbance of very low density lipoprotein (VLDL) metabolism that occurs as a result of intensive insulin treatment and during a euglycaemic clamp have been investigated in a rat model. Normal rats were maintained with fed blood glucose levels below 5 mmol l-1 for 8 weeks by subcutaneous insulin injections (normal fed levels 5.8 +/- 0.4 (SD) mmol l-1). Glucose requirement to maintain a glucose clamp was significantly reduced (116 +/- 3 mumol min-1 kg-1 (SE) vs. 173 +/- 5 mumol min-1 kg-1, P less than 0.001), compared with weight-matched normal control rats. In the fasting state (blood glucose 3.5 +/- 0.2 mmol l-1 vs. 3.9 +/- 0.1 mmol l-1, NS) plasma non-esterified fatty acid levels were reduced. Fasting VLDL-triglyceride turnover, measured by bolus injection of 14C-VLDL, was also lower (3.17 +/- 0.12 mumol min-1 kg-1 vs. 3.50 +/- 0.07 mumol min-1 kg-1, P less than 0.05). Despite decreased turnover, insulin over-treated rats had normal plasma triglyceride concentrations indicating a removal defect. At the end of a 3-h euglycaemic clamp, plasma triglyceride concentrations and VLDL-triglyceride turnover were decreased in both normal control and insulin over-treated animals, and turnover remained significantly lower in the insulin over-treated rats (2.59 +/- 0.13 mumol min-1 kg-1 vs. 3.08 +/- 0.10 mumol min-1 kg-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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The Effect of Diabetes Mellitus on Sterol Synthesis in the Intact Rat

Cited by 50 publications

References 7 publications

Lipogenesis From Ketone Bodies in Perfused Livers From Streptozocin-Induced Diabetic Rats

Lipogenesis From Ketone Bodies in Perfused Livers From Streptozocin-Induced Diabetic Rats

Dietary ω3 fatty acids and cholesterol modify enterocyte microsomal membrane phospholipids, cholesterol content and phospholipid enzyme activities in diabetic rats

Very low density lipoprotein metabolism after insulin over‐treatment and during a euglycaemic clamp

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