Document Detail


Physiological modulation of circulating FGF21: relevance of free fatty acids and insulin.
MedLine Citation:
PMID:  20424140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibroblast growth factor 21 (FGF-21), a novel metabolic factor in obesity and fasting metabolism, has been shown to be regulated by supraphysiological levels of free fatty acids (FFAs) under hyperinsulinemic conditions. Interestingly, it is still unclear whether the observed effects of FFAs on FGF-21 are relevant under physiological conditions, and the relative functions of FFAs and insulin within this context also need to be determined. Fourteen healthy men were studied in a randomized controlled crossover trial (RCT) using lipid heparin infusion (LHI) at a dose inducing physiological elevations of FFAs vs. saline heparin infusion. In a second randomized controlled trial, FGF-21 was analyzed in 14 patients with type 1 diabetes (6 men, 8 women) during continuous insulin supply vs. discontinued insulin infusion and subsequently increased lipolysis and ketosis. Circulating FGF-21 increased during physiologically elevated FFAs induced by LHI, which was accompanied by mild hyperinsulinemia. Interestingly, a mild elevation of FFAs resulting from complete insulin deficiency also increased FGF-21 levels. These results from two independent human RCTs suggest that FFAs increase circulating FGF-21, while insulin is only of minor importance under physiological conditions. This mechanism might explain the apparent paradox of increased FGF-21 levels in obesity, insulin resistance, and starvation.
Authors:
Knut Mai; Thomas Bobbert; Christian Groth; Anke Assmann; Sabine Meinus; Jessica Kraatz; Janin Andres; Ayman M Arafat; Andreas F H Pfeiffer; Matthias Möhlig; Joachim Spranger
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  299     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-07-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E126-30     Citation Subset:  IM    
Affiliation:
Department of Endocrinology, Diabetes, and Nutrition, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Glucose / metabolism
Cross-Over Studies
Diabetes Mellitus, Type 1 / blood*,  drug therapy
Fatty Acids, Nonesterified / physiology*
Female
Fibroblast Growth Factors / blood*
Heparin / administration & dosage
Humans
Insulin / administration & dosage*,  blood*
Insulin Resistance / physiology
Ketone Bodies / metabolism,  urine
Male
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Ketone Bodies; 0/fibroblast growth factor 21; 11061-68-0/Insulin; 62031-54-3/Fibroblast Growth Factors; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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