Effect of insulin detemir, compared to human insulin, on 3T3-L1 adipogenesis.
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 (P</=0.0033). MA did not reveal adipogenic properties, and MA pretreatment did not affect 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.
Böhm
Anja
A
Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen, D-72076 Tübingen, Germany.
Staiger
Harald
H
Hennige
Anita M
AM
Haas
Carina
C
Machicao
Fausto
F
Häring
Hans-Ulrich
HU
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D020738:Leptin / Q000235:genetics; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007328:Insulin; D049528:Insulin, Long-Acting; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D000069057:Insulin Detemir