Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Subiabre, Mario¹  Silva, Luis^1,2  Villalobos-Labra, Roberto¹  Toledo, Fernando^1,3  Paublo, Mario⁴  Lopez, Marcia A.⁴  Salsoso, Rocio^1,5  Pardo, Fabian^1,6  Leiva, Andrea¹  Sobrevia, Luis^1,5,7 

[1] Pontificia Univ Catolica Chile, Fac Med, Sch Med, Cellular & Mol Physiol Lab,Div Obstet & Gynaecol, POB 114-D, Santiago 8330024, Chile

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Immunoendocrinol,Div Med Biol, NL-9700 RB Groningen, Netherlands

[3] Univ Bio Bio, Fac Sci, Dept Basic Sci, Chillan 3780000, Chile

[4] Hosp San Juan Dios, Gynaecol & Obstet Serv, Santiago 8330024, Chile

[5] Univ Seville, Fac Pharm, Dept Physiol, E-41012 Seville, Spain

[6] Univ Valparaiso, Ctr Res Dev & Innovat Hlth Aconcagua Valley, Metab Dis Res Lab, Sch Med,Fac Med, San Felipe Campus, San Felipe 2172972, Chile

[7] Univ Queensland, Fac Med & Biomed Sci, Ctr Clin Res UQCCR, Herston, Qld 4029, Australia

关键词: Diabetes;    Insulin therapy;    Endothelium;    Arginine;    Nitric oxide;    Umbilical vein;   

DOI  :  10.1016/j.bbadis.2017.07.022

来源: Elsevier

【 摘 要 】

Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42(mapk) and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42(mapk), but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42(mapk) activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature.

【 授权许可】

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