Modeling Adipokine and Insulin-Mediated Crosstalk Between Adipocytes and Beta Cells Using Flow-Enabled Microfluidics.

Obesity-associated beta cell dysfunction is a crucial factor in the pathogenesis of Type 2 Diabetes (T2D), driven by a dysfunctional crosstalk between adipose tissues and pancreatic beta cells. Traditional culture systems cannot capture this crosstalk in a dynamic and controlled manner. A flow-enabled microfluidic is developed with an embedded micro-Tesla (µTesla) pump to assess the adipocyte-beta cell crosstalk. This recirculating system allows them to study the transport of soluble-factor-based between cultured 3T3 L1 adipocytes and INS1 beta cells. It is found that flow-enabled incubation with elevated glucose and insulin increased the levels of adipocyte-derived secretions of IL-6, TNF-α, and adiponectin in the media. In turn, adipocyte-derived IL-6 enhanced beta-cell insulin secretions in the same media, establishing a feed-forward loop. This mechanism can contribute to the hyperinsulinemia and pro-inflammatory conditions characteristic of obesity-related T2D. The findings highlight the advantages of flow-enabled microfluidics in modeling adipocyte-beta cell crosstalk in obesity, providing novel insights into obesity-associated beta cell dysfunction.