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Sponsored by: |
German Institute of Human Nutrition |
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Information provided by: | German Institute of Human Nutrition |
ClinicalTrials.gov Identifier: | NCT00277342 |
The investigators hypothesise that a common A277G polymorphism of the liver fatty acid binding protein (L-FABP) gene, which leads to an amino acid exchange, may be associated with alterations of lipid-induced hepatic insulin resistance. In the present study the investigators will investigate potential differences in lipid-induced hepatic insulin resistance, and in the relation between glycogenolysis and gluconeogenesis, in healthy subjects with the A277G polymorphism vs. subjects carrying the wildtype.
Condition | Intervention |
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Wildtype Polymorphism Liver FABP |
Procedure: measurement of lipid-induced hepatic insulin resistance |
Study Type: | Interventional |
Study Design: | Diagnostic, Randomized, Single Blind, Placebo Control, Single Group Assignment |
Estimated Enrollment: | 18 |
Study Start Date: | January 2006 |
Estimated Study Completion Date: | April 2006 |
Liver fatty acid binding protein (L-FABP) is an abundant cytosolic lipid-binding protein that regulates lipid transport and metabolism. Only one common non-synonymous polymorphism (A227G) leading to an amino-acid exchange in the exonic region of the L-FABP gene has been previously identified. Experimental elevations of free fatty acids (FFAs) have been shown to impair insulin mediated suppression of endogenous glucose production (EGP).
Deletion of the L-FABP gene shows no obvious phenotype in mice receiving a low fat chow diet, but leads to decreased hepatic triglyceride accumulation in the prolonged fasted state, which exposes mice to an increased fatty acid flux to the liver. The function of the L-FABP gene may be altered by polymorphisms in coding regions of the gene, probably leading to modifications in hepatic triglyceride accumulation and hepatic insulin resistance.We hypothesize that carriers of the A277G SNP, when compared to matched wild-type subjects, may show altered responses of hepatic glucose production upon exposure to increased peripheral fatty acid concentrations, as achieved by lipid / heparin infusions. Because it is known that free fatty acids potently increase insulin secretion, we use somatostatin clamps in our experiments, followed by replacement of postabsorptive insulin and glucagon concentrations.
Ages Eligible for Study: | 18 Years to 70 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Germany | |
German Institute of Human Nutrition DIfE, Dpt. of Clinical Nutrition, Potsdam-Rehbrücke | |
Nuthetal, Germany, 14558 |
Principal Investigator: | Martin O Weickert, MD | German Institute of Human Nutrition; Charité Campus Benjamin Franklin |
Principal Investigator: | Matthias Möhlig, MD | German Institute of Human Nutrition; Charité Campus Benjamin Franklin |
Study Chair: | Andreas FH Pfeiffer, MD | German Institute of Human Nutrition; Charité Campus Benjamin Franklin |
Study ID Numbers: | MOW_MM_LFABP |
Study First Received: | January 12, 2006 |
Last Updated: | August 6, 2008 |
ClinicalTrials.gov Identifier: | NCT00277342 History of Changes |
Health Authority: | Germany: Ethics Commission |
lipid induced hepatic insulin resistance polymorphisms liver fatty-acid-binding-protein gluconeogenesis glycogenolysis endogenous glucose production |
Hyperinsulinism Hypoglycemic Agents Metabolic Diseases Insulin Resistance |
Glucose Metabolism Disorders Metabolic Disorder Insulin |
Hyperinsulinism Hypoglycemic Agents Metabolic Diseases Physiological Effects of Drugs |
Insulin Resistance Glucose Metabolism Disorders Pharmacologic Actions Insulin |