Effect of insulin detemir, compared to human insulin, on 3T3-L1 adipogenesis.

ABSTRACT

Insulin detemir (DET) represents a myristic acid (MA)-coupled insulin derivative with protracted action due to reversible albumin binding. As compared to human insulin (HI), DET provokes no or only minor body weight gain in vivo. Therefore, we compared DET's and HI's adipogenic effects. 3T3-L1 preadipocytes were differentiated with 5 nmol/l HI, 5 nmol/l DET (=DET(equimolar)), or 20 nmol/l DET (=DET(equipotent); equipotent in terms of the reported metabolic potency in vitro). Due to differentiation-suppressive effects, albumin was excluded from the studies. During the induction period, only HI allowed clonal expansion. Moreover, HI induced a 200-fold increase in specific glycerol-3-phosphate dehydrogenase activity, whereas DET(equimolar) and DET(equipotent) were markedly less adipogenic (Paffect HI- or DET(equipotent)-induced adipogenesis. These results were closely reflected at the level of marker gene expression (PPARgamma2, leptin) and morphology (Oil Red O-stained intracellular lipids). We conclude that DET displays reduced adipogenity, and this could contribute to DET's weight-sparing effect in vivo.