| Regulation of diurnal variation of cholesterol 7alpha-hydroxylase (CYP7A1) activity in healthy subjects. | |
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MedLine Citation:
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PMID: 19537927 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three day-long examinations were carried out in 12 healthy men. The concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans. |
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Authors:
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J Kovár; M Lenícek; M Zimolová; L Vítek; M Jirsa; J Pitha |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-19 |
Journal Detail:
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Title: Physiological research / Academia Scientiarum Bohemoslovaca Volume: 59 ISSN: 0862-8408 ISO Abbreviation: Physiol Res Publication Date: 2010 |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-08-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9112413 Medline TA: Physiol Res Country: Czech Republic |
Other Details:
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Languages: eng Pagination: 233-8 Citation Subset: IM |
Affiliation:
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Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jan.kovar@medicon.cz |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anticholesteremic Agents / administration & dosage Bile Acids and Salts / metabolism* Blood Glucose / metabolism* Chenodeoxycholic Acid / administration & dosage Cholestenones / blood Cholesterol / blood Cholesterol 7-alpha-Hydroxylase / metabolism* Cholestyramine Resin / administration & dosage Circadian Rhythm / physiology* Enzyme Activation Fatty Acids, Nonesterified / blood Gastrointestinal Agents / administration & dosage Humans Insulin / blood* Male Reference Values Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Bile Acids and Salts; 0/Blood Glucose; 0/Cholestenones; 0/Fatty Acids, Nonesterified; 0/Gastrointestinal Agents; 0/Triglycerides; 11041-12-6/Cholestyramine Resin; 11061-68-0/Insulin; 3862-25-7/7 alpha-hydroxy-4-cholesten-3-one; 474-25-9/Chenodeoxycholic Acid; 57-88-5/Cholesterol; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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