Cholesterol biosynthesis in nonketotic diabetics before and during insulin therapy

Andersen, Eva; Hellström, Per M.; Hellström, Kjell

doi:10.1016/s0168-8227(87)80041-4

Cited by 19 publications

(13 citation statements)

References 22 publications

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“…Data from clinical and experimental studies show an altered synthesis and transport of bile acids in diabetes (4,5). Moreover, hypertriglyceridemia is one of the most frequent lipid abnormalities that is also positively associated with gall bladder disease (1).…”

Section: Discussionmentioning

confidence: 99%

“…High serum triglyceride levels, often present in type 2 diabetes, have been positively associated with gall bladder disease risk (1), a highly prevalent pathology in diabetic patients (2,3). In addition, alterations in bile composition have been described in diabetic patients (4,5). However, the molecular link between bile acid metabolism and triglyceride homeostasis in diabetes or insulin resistance remains to be determined.…”

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confidence: 99%

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Glucose Regulates the Expression of the Farnesoid X Receptor in Liver

et al. 2004

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Glucose Regulates the Expression of the Farnesoid X Receptor in Liver

et al. 2004

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“…This is in agreement with other observations that insulin therapy depresses the rate of cholesterologenesis in patients with non-insulin-dependent diabetes mellitus. 41 Also, increased cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase activity 42 were previously demonstrated in MPM from insulin-deficient mice. In that study, insulin addition resulted in reduced HMGCoA-reductase activity and reduced cholesterol biosynthesis.…”

Section: Shamir Et Almentioning

confidence: 96%

Oral Insulin Supplementation Attenuates Atherosclerosis Progression in Apolipoprotein E-Deficient Mice

Shamir

Shehadeh²,

Eshach-Adiv³

et al. 2003

ATVB

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Objective-The role of insulin in atherosclerosis progression in diabetes is uncertain. We examined the effects of oral insulin supplementation on atherogenesis in apolipoprotein E-deficient (E 0 ) mice. Methods and Results-One-month-old male E 0 mice were orally supplemented with human insulin (0.1, 0.5, and 1 U/mL) or placebo for 3 months. At the end of the study, serum and macrophage oxidative stress and atherosclerosis progression were studied. Insulin reduced lesion size by 22% to 37% (PϽ0.05) in all study groups. Lipid peroxides serum levels were 18% lower (PϽ0.01), and serum paraoxonase activity was 30% higher (PϽ0.01) in mice supplemented with 1.0 U/mL insulin compared with controls. Insulin reduced mouse peritoneal macrophage (MPM) lipid peroxides content and superoxide anion release by up to 44% and 62%, respectively (PϽ0.01). In addition, oral insulin reduced MPM cholesterol content and cholesterol biosynthesis by up to 36% and 53%, respectively (PϽ0.01). In vitro incubation of E 0 mice MPM with increasing insulin concentrations (0 to 100 U/mL) resulted in a dose-dependent reduction of cholesterol synthesis by up to 66% (PϽ0.05). Conclusions-In

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“…Subsequently, changes in bile acid pool composition have been demonstrated in both animal models of type 1 diabetes and type 2 diabetes, respectively (132,133,134,135), as well as in early (131,136,137,138,139) and recent human studies (22, 111, 121, 140). Of note, both glucose (141) and insulin have been suggested to modulate bile acid synthesis in preclinical studies (135,142,143) and in some (131,138,144), but not all (137), clinical studies. As noted by Staels & Fonseca, the finding that insulin is able to suppress FXR (NR1H4) gene expression (in contrast to glucose, which produces the opposite effect) suggests that diabetes is associated with the dysregulation of FXR expression (141,145).…”

Section: Bile Acid Pool Composition Is Altered In Type 2 Diabetesmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

Sonne

Hansen

Knop

2014

European Journal of Endocrinology

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Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently -despite elusive mechanisms of action -bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

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Cholesterol biosynthesis in nonketotic diabetics before and during insulin therapy

Cited by 19 publications

References 22 publications

Glucose Regulates the Expression of the Farnesoid X Receptor in Liver

Glucose Regulates the Expression of the Farnesoid X Receptor in Liver

Oral Insulin Supplementation Attenuates Atherosclerosis Progression in Apolipoprotein E-Deficient Mice

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

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