RGD Reference Report - Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis? - Rat Genome Database

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Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis?

Authors: Arafat, AM  Kaczmarek, P  Skrzypski, M  Pruszynska-Oszmalek, E  Kolodziejski, P  Szczepankiewicz, D  Sassek, M  Wojciechowicz, T  Wiedenmann, B  Pfeiffer, AF  Nowak, KW  Strowski, MZ 
Citation: Arafat AM, etal., Diabetologia. 2013 Mar;56(3):588-97. doi: 10.1007/s00125-012-2803-y. Epub 2012 Dec 22.
RGD ID: 10401916
Pubmed: PMID:23262585   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-012-2803-y   (Journal Full-text)

AIMS/HYPOTHESIS: Glucagon reduces body weight by modifying food intake, glucose/lipid metabolism and energy expenditure. All these physiological processes are also controlled by fibroblast growth factor 21 (FGF-21), a circulating hepatokine that improves the metabolic profile in obesity and type 2 diabetes. Animal experiments have suggested a possible interaction between glucagon and FGF-21 however, the metabolic consequences of this crosstalk are not understood. METHODS: The effects of exogenous glucagon on plasma FGF-21 levels and lipolysis were evaluated in healthy volunteers and humans with type 1 diabetes, as well as in rodents with streptozotocin (STZ)-induced insulinopenic diabetes. In vitro, the role of glucagon on FGF-21 secretion and lipolysis was studied using isolated primary rat hepatocytes and adipocytes. Fgf-21 expression in differentiated rat pre-adipocytes was suppressed by small interfering RNA and released FGF-21 was immunoneutralised by polyclonal antibodies. RESULTS: Glucagon induced lipolysis in healthy human volunteers, patients with type 1 diabetes, mice and rats with STZ-induced insulinopenic diabetes, and in adipocytes isolated from diabetic and non-diabetic animals. In addition, glucagon increased circulating FGF-21 in healthy humans and rodents, as well as in patients with type 1 diabetes, and insulinopenic rodents. Glucagon stimulated FGF-21 secretion from isolated primary hepatocytes and adipocytes derived from animals with insulinopenic diabetes. Furthermore, FGF-21 stimulated lipolysis in primary adipocytes isolated from non-diabetic and diabetic rats. Reduction of Fgf-21 expression (by approximately 66%) or immunoneutralisation of released FGF-21 markedly attenuated glucagon-stimulated lipolysis in adipocytes. CONCLUSIONS/INTERPRETATION: These results indicate that glucagon increases circulating FGF-21 independently of endogenous insulin levels. FGF-21 participates in glucagon-induced stimulation of lipolysis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOFgf21 (Rattus norvegicus)10401916; 10401916protein:decreased expression:serum:RGD 
Experimental Diabetes Mellitus  ISOFgf21 (Mus musculus)10401916; 10401916protein:decreased expression:serum:RGD 
Experimental Diabetes Mellitus  IEP 10401916; 10401916protein:decreased expression:serum:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to glucagon stimulus  IEP 10401916 RGD 
positive regulation of triglyceride catabolic process  IMP 10401916 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fgf21  (fibroblast growth factor 21)

Genes (Mus musculus)
Fgf21  (fibroblast growth factor 21)

Genes (Homo sapiens)
FGF21  (fibroblast growth factor 21)


Additional Information