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.
Highlights
Diabetes is one of the most abundantly spread metabolic diseases worldwide and one of the leading causes of death, remaining without effective treatment methods
The results revealed that the secretory pattern in response to LPC with various fatty acyl chains was comparable for MIN6 and MIN6-MS1 PIs
Our studies evaluated whether the formation of homotypic PIs composed solely of β cells would be effective in restoring the high Gpr40 expression level
Summary
Diabetes is one of the most abundantly spread metabolic diseases worldwide and one of the leading causes of death, remaining without effective treatment methods. The antidiabetic monotherapies are still deficient in maintaining long-term glycemic regulation and are coupled with side effects [1]. There is a constant need for the development of alternative medication [2]. On the other hand, selecting appropriate cell models for in vitro development of pancreatic islet model which would resemble natural islets of Langerhans more closely, is challenging. The majority of research completed to date has used rodent pancreatic β cell lines due to their immortality and stimulus-induced insulin-secretion [3]. Murine (e.g., MIN6, NIT-1, βTC, and βHC clones) and rat (e.g., RIN, INS-1)
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