A 3D co-culture intestinal organoid system for exploring glucose metabolism

Abstract

Many treatments have been used for glucose metabolism diseases such as type 2 diabetes, and all of those treatments have several advantages as well as limitations. This review introduces a 3D co-culture intestinal organoid system developed from stem cells, which has the special function of simulating human tissues. Recent studies have revealed that the gut is an important site for exploring the interactions among glucose metabolism, gut microbial metabolism, and gut microbiota. Therefore, 3D intestinal organoid systems can be used to imitate the congenital errors of human gut development, drug screening, food transportation and toxicity analysis. The intestinal organoid system construction methods and their progress as compared with traditional 2D culture methods have also been summarised in the manuscript. This paper discusses the research progress in terms of intestinal organoids applicable to glucose metabolism and provides new ideas for developing anti-diabetic drugs with high efficiency and low toxicity.

Keywords: 3D co-culture; Glucose metabolism; Intestinal organoid.

Graphical abstract

Fig. 1

Application of intestinal organoids in the treatment of diabetes.

Fig. 2

Culturing of the human islet organoids.

Fig. 3

The Wnt/β-Catenin Signalling Pathway. Abbreviations: LRP5/6, low-density lipoprotein receptor-related protein 5/6; FZD, frizzled; β-cat, β-catenin; P, phosphorylation; R-spo, R-spondin; CK, casein kinase; GSK, glycogen synthase kinase; Dvl, Dishevelled; APC, adenomatous polyposis coli; TCF/LEF, T cell factor/lymphoid enhancer-binding factor; RNF43, RING finger protein 43; LGR5, leucine-rich-repeat containing G-protein coupled receptor 5.

Fig. 4

Human intestinal organoid culture and induction of diabetic intestinal organoids.

Fig. 5

Intestinal microbiota in homeostasis and dysbiosis and an overview of the intestinal microbiota promoting insulin secretion.