Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane

Abstract

: Insulin stimulates glucose transporter 4 (GLUT4) vesicle recruitment from its intracellular storage site to the plasma membrane. Cysteine string protein 1 (CSP1) is a SNARE-binding protein involved in the vesicular trafficking of neurotransmitters and other exocytic processes. In this study, we investigated the involvement of CSP1 in insulin-dependent GLUT4 recruitment in 3T3-L1 adipocytes. Over-expression of wild-type CSP1 led to attenuated insulin-stimulated glucose uptake without any change in GLUT4 content in the plasma membrane, rather it inhibits docking by blocking the association of VAMP2 with syntaxin 4. In contrast, knockdown of CSP1 enhanced insulin-stimulated glucose uptake. The mRNA and protein expression of CSP1 was elevated in 3T3-L1 adipocytes in insulin resistant states caused by high levels of palmitate and chronic insulin exposure. Taken together, the results of this study suggest that CSP1 is involved in insulin resistance by interrupting GLUT4 vesicle docking with the plasma membrane.

Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol

“…Elevated circulating estrogen levels have been related to insulin resistance in pregnancy ( 39 ). After binding to the estrogen receptor, estradiol may decrease insulin sensitivity through reducing the expression of the insulin sensitive membrane transporter - glucose transporter 4 in adipose tissue and muscle ( 40 , 41 ). Two studies on cord blood estradiol levels in GDM showed inconsistent findings ( 42 , 43 ).…”