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LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance
- Source :
- Diabetes. 63(5)
- Publication Year :
- 2014
-
Abstract
- Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance. © 2014 by the American Diabetes Association.
- Subjects :
- medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Carbohydrate metabolism
Severity of Illness Index
Mice
Insulin resistance
Internal medicine
Internal Medicine
medicine
Myocyte
Animals
Humans
Insulin
Obesity
Phosphorylation
Protein kinase A
Muscle, Skeletal
Muscle Cells
biology
Skeletal muscle
medicine.disease
Insulin receptor
Endocrinology
medicine.anatomical_structure
Glucose
Liver
biology.protein
Hepatocytes
Intercellular Signaling Peptides and Proteins
Signal transduction
Insulin Resistance
Signal Transduction
Subjects
Details
- ISSN :
- 1939327X
- Volume :
- 63
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....1b9bfdcdcde53416f8bd683146ab074d