Lipasin Ameliorates Insulin Resistance in Gestational Diabetes Mellitus by Activating the SREBP1/AMPK Signaling Pathway
Abstract
Objective: : To investigate the effect of Lipasin (also known as angiopoietin-like protein 8 [ANGPTL8] or betatrophin) on insulin resistance (IR) in gestational diabetes mellitus (GDM) and its underlying molecular mechanisms, thereby providing a new theoretical basis for the clinical diagnosis and treatment of GDM.
Methods:: (1) The GEO database was mined to analyze Lipasin expression in pregnant women with GDM versus those with normal glucose tolerance (NGT). (2) Serum, umbilical cord blood, and placental tissues were collected from GDM and NGT women to detect Lipasin expression levels. (3) Lipasin-overexpressing and Lipasin-knockout Hep G2 cell models were established, and glucose uptake capacity was assessed under high-insulin conditions, with or without AMP-activated protein kinase (AMPK) inhibitor (Compound C) intervention. (4) Proteomic analysis was performed to identify IR-related signaling pathway changes, and SREBP1 protein expression was measured. (5) Western blotting (WB) was used to detect the expression of PCK2, GLUT4, SREBP1, and AMPK phosphorylation in WT, Lipasin-OE, and Lipasin-KO IR cells. Additionally, WT and Lipasin-KO IR cells were treated with 5 mM metformin for 24 h to evaluate its effect on Lipasin expression and AMPK phosphorylation, thereby exploring the potential involvement of the Lipasin/AMPK axis in metformin-mediated glucose regulation.
Results:: •GEO database analysis revealed significantly elevated Lipasin levels in the umbilical cord blood…
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