Abstract
Beta cell failure is one of the most important features of type 2 diabetes mellitus (T2DM). High‐density lipoprotein (HDL) has been proposed to improve β‐cell function. However, the mechanisms involved in this process are still poorly understood. The aim of this study was to investigate the contribution of sphingosine‐1‐phosphate (S1P) in the impact of HDL treatment on insulin secretion by pancreatic β‐cells and to determine its mechanisms. Primary cultures of β‐cells isolated from rat were treated with or without HDL in the presence or absence of S1P pathway inhibitors and insulin secretion response was analyzed. The S1P content of HDL (HDL‐S1P) isolated from T2DM patients was analyzed and correlated to the HDL‐induced insulin secretion. The expression of genes involved in the biosynthesis of the insulin was also evaluated. HDL as well as S1P treatment enhanced glucose‐stimulated insulin secretion (GSIS). In HDL isolated from T2DM patients, while HDL‐S1P was strongly correlated to its pro‐secretory capacity (r = 0.633, p = 0.005), HDL‐cholesterol and apolipoprotein AI levels were not. HDL‐induced GSIS was blocked by the S1P1/3 antagonist but not by the S1P2 antagonist, and was also accompanied by increased intracellular S1P in β‐cells. We also observed that HDL improved GSIS without significant changes in expression levels of insulin biosynthesis genes. Our present study highlights the importance HDL‐S1P in GSIS in T2DM patients and demonstrates that HDL induces insulin secretion by a process involving both intra‐ and extra‐cellular sources of S1P independently of an effect on insulin biosynthesis genes.
Highlights
Consistent with other reports, our glucose-stimulated insulin secretion (GSIS) analysis performed on pancreatic β-cells revealed that treatment with High-density lipoprotein (HDL) (400 μg/ ml) for 24 h doubled insulin secretion compared to non-treated cells (Figure 1a)
The authors concluded that effects of HDL on pancreatic β-cells were principally explained by a protective impact on cell survival against stress-induced apoptosis, as promoted by high glucose concentrations and cytokines (Petremand et al, 2009, 2012; Rutti et al, 2009)
A direct role for HDL in insulin secretion has been poorly explored some studies propose a role for apolipoprotein AI (apoAI) (Rye et al, 2016)
Summary
A total number of 18 T2DM patients were prospectively recruited at the University Hospitals of Geneva, Service of Therapeutic Education for Chronic Diseases. Prior to testing GSIS, β-c ells were incubated 24 h with or without HDL (400 μg/ml) in DMEM containing 0.5% fatty acid-free bovine serum albumin (BSA), 5.6 mM D- glucose and antibiotics (see Figure S2 for experimental protocol). HDL (d = 1.063–1.21 g/ml) was prepared by a standard double ultracentrifugation protocol from pooled human plasma of healthy donors as described (Brinck et al, 2016). To evaluate whether S1P contained in HDL particle was able to transfer into cultured β-cells, β-cells were incubated 24 h with or without HDL particles (400 μg/ml) that contained S1Pd7 in DMEM containing 0.5% free fatty acid bovine serum albumin (BSA), 5.6 mm D-g lucose and antibiotics (see Figure S2d for experimental protocol). A value of p < 0.05 was considered significant
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
