Investigation of insulin resistance through a multiorgan microfluidic organ-on-chip

Abstract

The development of hepatic insulin resistance (IR) is a critical factor in developing type 2 diabetes (T2D), where insulin fails to inhibit hepatic glucose production but retains its capacity to promote hepatic lipogenesis. Improving insulin sensitivity can be effective in preventing and treating T2D. However, selective control of glucose and lipid synthesis has been difficult. It is known that excess white adipose tissue is detrimental to insulin sensitivity, whereas brown adipose tissue transplantation can restore it in diabetic mice. However, challenges remain in our understanding of liver-adipose communication because the confounding effects of hypothalamic regulation of metabolic function cannot be ruled out in previous studies. There is a lack of in vitro models that use primary cells to study cellular-crosstalk under insulin resistant conditions. Building upon our previous work on the microfluidic primary liver and adipose organ-on-chips, we report for the first time the development of integrated insulin resistant liver-adipose (white and brown) organ-on-chip. The design of the microfluidic device was carried out using computational fluid dynamics; the experimental studies were conducted by carrying out detailed biochemical analysis RNA-seq analysis on both cell types. Further, we tested the hypothesis that brown adipocytes regulated both hepatic insulin sensitivity and lipogenesis. Our results show effective co-modulation of hepatic glucose and lipid synthesis through a platform for identifying potential therapeutics for IR and diabetes.

[Retracted] Application of CFD Numerical Simulation Image Imaging Technology in the Study of Droplet Microfluidic Multiphase Flow Characteristics

“…At present, there is no unified formulation on the division of scale. Generally, the scale greater than 1 mm is called macro scale, and the scale of 1 um-1 mm is called micro scale [ 7 ]. Kimet al found that the configuration of the microfluidic liquid-liquid extraction chip channel usually adopts double Y -type two-phase laminar flow or double type three-phase laminar flow.…”