Amylin stimulates fatty acid esterification in 3T3-L1 adipocytes

Amylin is co-localized and co-secreted with insulin, however its direct effects on adipocytes are unexplored. In 3T3-L1 preadipocytes, amylin increased thymidine incorporation (174%; p < 0.05) and Myc mRNA expression (378%; p < 0.01). Amylin supplementation during differentiation enhanced triglyceride accumulation (272%; p < 0.001). In 3T3-L1 adipocytes, amylin increased fatty acid uptake (238%; p < 0.01) and further potentiated the effects of insulin (insulin 158%; p < 0.01, amylin + insulin 335%; p < 0.001 vs CTL, p < 0.001 vs insulin). By contrast, amylin inhibited glycerol release in 3T3-L1 adipocytes (−50%; p < 0.05) and primary adipocytes (−34%; p < 0.05). Amylin stimulated cytokine secretion (monocyte chemotactic protein-1 + 166%, keratinocyte-derived chemokine + 174%; both p < 0.05) and mRNA expression of PPARγ (163%; p < 0.01), C/EBPβ (121%, p < 0.05), DGAT1 (157%; p < 0.01), FABP4 (122%; p < 0.01), and CD36 (122%; p < 0.05). In human adipose tissue, mRNA expression of amylin receptor genes (CALCR and RAMP3) correlated with numerous lipid and insulin signaling genes, plasma glucose and HOMA. Altogether amylin directly stimulates fat cells, potentiates the effects of insulin and may influence insulin resistance.