Targeting Adrenomedullin to Improve Lipid Homeostasis in Diabetic Pregnancies

靶向肾上腺髓质素来改善糖尿病妊娠的脂质稳态

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作者:Yuanlin Dong, Ancizar Betancourt, Michael Belfort, Chandrasekhar Yallampalli

Conclusions

GDM pregnancies are associated with increased AM and its receptor expression in adipose tissues. AM stimulates lipolysis and leptin and resistin expression, and these effects can be reversed by AM antagonist. To our knowledge, manipulation of AM and its receptors in adipocytes might represent an approach in reducing the risk of GDM and fetal overgrowth.

Results

AM and its receptor components, calcitonin receptor-like receptor, receptor activity-modifying protein 2, and receptor activity-modifying protein 3, were higher in adipose tissues from GDM compared with NGT pregnancies, and these expressions in normal adipose tissues were enhanced by glucose and tumor necrosis factor-αin vitro. AM dose- and time-dependently stimulated lipolysis in human adipocytes, and this effect was reversed by AM antagonist AM22-52. Furthermore, AM inhibited phosphorylation of insulin receptor-β and insulin receptor substrate-1 and enhanced the protein expression of leptin and resistin in adipose tissue from NGT women. The increased messenger RNA expression of leptin and resistin in adipose tissue from GDM was reduced by AM22-52 treatment. Conclusions: GDM pregnancies are associated with increased AM and its receptor expression in adipose tissues. AM stimulates lipolysis and leptin and resistin expression, and these effects can be reversed by AM antagonist. To our knowledge, manipulation of AM and its receptors in adipocytes might represent an approach in reducing the risk of GDM and fetal overgrowth.

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