Simulated Cholinergic Reinnervation of β (INS-1) Cells: Antidiabetic Utility of Heterotypic Pseudoislets Containing β Cell and Cholinergic Cell

International Journal of Endocrinology
Ao JiaoJialin Zhang

Abstract

Cholinergic neurons can functionally support pancreatic islets in controlling blood sugar levels. However, in islet transplantation, the level of cholinergic reinnervation is significantly lower compared to orthotopic pancreatic islets. This abnormal reinnervation affects the survival and function of islet grafts. In this study, the cholinergic reinnervation of beta cells was simulated by 2D and 3D coculture of INS-1 and NG108-15 cells. In 2D culture conditions, 20 mM glucose induced a 1.24-fold increase (p < 0.0001) in insulin secretion from the coculture group, while in the 3D culture condition, a 1.78-fold increase (p < 0.0001) in insulin secretion from heterotypic pseudoislet group was observed. Glucose-stimulated insulin secretion (GSIS) from 2D INS-1 cells showed minimal changes when compared to 3D structures. E-cadherin expressed in INS-1 and NG108-15 cells was the key adhesion molecule for the formation of heterotypic pseudoislets. NG108-15 cells hardly affected the proliferation of INS-1 cells in vitro. Heterotypic pseudoislet transplantation recipient mice reverted to normoglycemic levels faster and had a greater blood glucose clearance compared to INS-1 pseudoislet recipient mice. In conclusion, cholinergic cells can...Continue Reading

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Citations

Aug 28, 2020·Transplant International : Official Journal of the European Society for Organ Transplantation·Charles-Henri WassmerEkaterine Berishvili
Aug 18, 2020·BioMed Research International·Ao JiaoXiangdong Hua
Oct 8, 2020·Médecine sciences : M/S·Fanny LebretonEkaterine Berishvili
Mar 4, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Jingjun LiLin Zhou

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Methods Mentioned

BETA
ELISA
Assay
light microscopy

Software Mentioned

GraphPad Prism
Image Lab

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