Formation of βTC3 and MIN6 Pseudoislets Changes the Expression Pattern of Gpr40, Gpr55, and Gpr119 Receptors and Improves Lysophosphatidylcholines-Potentiated Glucose-Stimulated Insulin Secretion

Abstract

The impaired spatial arrangement and connections between cells creating islets of Langerhans as well as altered expression of G protein-coupled receptors (GPCRs) often lead to dysfunction of insulin-secreting pancreatic β cells and can significantly contribute to the development of diabetes. Differences in glucose-stimulated insulin secretion (GSIS) are noticeable not only in diabetic individuals but also in model pancreatic β cells, e.g., βTC3 and MIN6 β cell lines with impaired and normal insulin secretion, respectively. Now, we compare the ability of GPCR agonists (lysophosphatidylcholines bearing fatty acid chains of different lengths) to potentiate GSIS in βTC3 and MIN6 β cell models, cultured as adherent monolayers and in a form of pseudoislets (PIs) with pancreatic MS1 endothelial cells. Our aim was also to investigate differences in expression of the GPCRs responsive to LPCs in these experimental systems. Aggregation of β cells into islet-like structures greatly enhanced the expression of Gpr40, Gpr55, and Gpr119 receptors. In contrast, the co-culture of βTC3 cells with endothelial cells converted the GPCR expression pattern closer to the pattern observed in MIN6 cells. Additionally, the efficiencies of various LPC species in βTC3-MS1 PIs also shifted toward the MIN6 cell model.

Isoprenoid Derivatives of Lysophosphatidylcholines Enhance Insulin and GLP-1 Secretion through Lipid-Binding GPCRs

“…Since similar ligands (LCFAs) also target GPR120 [ 7 ], we included the latter in the analysis. Previously, we confirmed GPR40, GPR55, and GPR119 expression in a MIN6 cell line [ 12 ], and the expression of GPR120 was also identified in this cell line [ 20 ].…”

“…Our previous studies indicated that in MIN6 cells LPCs with lauroyl (12:0), mirystoyl (14:0), palmitoyl (16:0), stearolyl (18:0), and oleoyl (18:1) fatty acid residues significantly potentiated the level of GSIS above the control level (from 1.5 to 3.5-fold). In this case, LPCs bearing longer acyl chains tended to stimulate MIN6 cells stronger than those bearing medium acyl chains [ 12 ]. Additionally, we demonstrated that LPC bearing oleoyl and palmitoyl fatty acid residues augmented GSIS by targeting GPR40, GPR55, and GPR119 receptors, which represent a novel antidiabetic approach [ 12 , 13 ].…”

“…In this case, LPCs bearing longer acyl chains tended to stimulate MIN6 cells stronger than those bearing medium acyl chains [ 12 ]. Additionally, we demonstrated that LPC bearing oleoyl and palmitoyl fatty acid residues augmented GSIS by targeting GPR40, GPR55, and GPR119 receptors, which represent a novel antidiabetic approach [ 12 , 13 ]. Moreover, we identified new insulin secretion modulators synthesized by combining the structures of two natural compounds, namely O -methyl derivatives of phenolic acids and LPC.…”

Trans-palmitoleic acid, a dairy fat biomarker, stimulates insulin secretion and activates G protein-coupled receptors with a different mechanism from the cis isomer

“…29 We have previously demonstrated the expression of Gpr40 , Gpr55 , and Gpr119 in MIN6 cells. 47 Here, we have detected all transcripts in both cell lines studied. In MIN6 cells Gpr40 mRNA was the most abundant, followed by Gpr120 .…”

Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope

“…The increase in BBB permeability produced by FFA1 receptor activation is significant given the fact that the endogenous agonist of the receptor, DHA is present in the diet, dietary supplements, and component of lipid-lowering drugs [3,4]. Lysophosphatidylcholine (LPC), an endogenous ligand for GPR119 receptor, has also been reported to exert some of its metabolic effects by activating FFA1/GPR40 and GPR55 [54][55][56]. Moreover, FFA1-selective agonists are still being considered as potential therapeutic agents for the treatment of metabolic disorders such as type 2 diabetes [57][58][59].…”