High-glucose 3D INS-1 cell model combined with a microfluidic circular concentration gradient generator for high throughput screening of drugs against type 2 diabetes

Abstract

In vitro models for screening of drugs against type 2 diabetes are crucial for the pharmaceutical industry. This paper presents a new approach for integration of a three-dimensionally-cultured insulinoma cell line (INS-1 cell) incubated in a high concentration of glucose as a new model. In this model, INS-1 cells tended to aggregate in the 3D gel (basement membrane extractant, BME), in a similar way to 3D in vivo cell culture models. The proliferation of INS-1 cells in BME was initially promoted and then suppressed by the high concentration of glucose, and the function of insulin secretion also was initially enhanced and then inhibited by the high concentration of glucose. These phenomena were similar to hyperglycemia symptoms, proving the validity of the proposed model. This model can help find the drugs that stimulate insulin secretion. Then, we identified the difference between the new model and the traditional two-dimensional model in terms of cell morphology, inhibition rate of cell proliferation, and insulin secretion. Simultaneously, we developed a circular drug concentration gradient generator based on microfluidic technology. We integrated the high-glucose 3D INS-1 cell model and the circular concentration gradient generator in the same microdevice, tested the utility of this microdevice in the field of drug screening with glipizide as a model drug, and found that the microdevice was more sensitive than the traditional device to screen the anti-diabetic drugs.