Obesity-related insulin resistance is linked to a chronic state of systemic and adipose-tissue-derived inflammation. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone also acting on adipocytes. We investigated if GIP affects inflammation, lipolysis and insulin resistance in human adipocytes. Human subcutaneous preadipocyte-derived adipocytes, differentiated in vitro, were treated with human GIP to analyze mRNA expression and protein secretion of cytokines, glycerol and free fatty acid release and insulin-induced glucose uptake. GIP induced mRNA expression of interleukin (IL)-6, IL-1β and of the IL-1 receptor antagonist IL-1Ra while tumor necrosis factor (TNF)-α, IL-8 and monocyte chemotactic protein (MCP)-1 remained unchanged. Cytokine induction involved the protein kinase A (PKA) and the NF-κB pathway as well as an autocrine IL-1 effect. Furthermore, GIP potentiated IL-6 and IL-1Ra secretion in the presence of lipopolysaccharide-, IL-1β- and TNF-α. GIP-induced lipolysis via activation of hormone-sensitive lipase and was linked to NF-κB activation. Finally, chronic GIP treatment impaired insulin-induced glucose uptake possibly due to the observed impaired translocation of glucose transporter type (GLUT)-4. In conclusion, GIP induces an inflammatory and pro-lipolytic response via the PKA - NF-κB - IL-1 pathway and impairs insulin sensitivity of glucose uptake in human adipocytes.
- glucose-dependent insulinotropic polypeptide (GIP)
- insulin resistance
- human adipocytes
- Copyright © 2012, American Journal of Physiology - Endocrinology and Metabolism