Orabi Mohamad, Yeganeh Mehdi Sh, Chun Tae-Hwa, Lo Joe Fujiou
Department of Mechanical Engineering, University of Michigan Dearborn, 4901 Evergreen Road, Dearborn, MI, 48128, USA.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Small. 2025 Sep;21(35):e2504686. doi: 10.1002/smll.202504686. Epub 2025 Jul 31.
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.
肥胖相关的β细胞功能障碍是2型糖尿病（T2D）发病机制中的关键因素，由脂肪组织和胰腺β细胞之间功能失调的相互作用驱动。传统的培养系统无法以动态和可控的方式捕捉这种相互作用。一种带有嵌入式微特斯拉（µTesla）泵的流动微流控装置被开发出来，用于评估脂肪细胞与β细胞之间的相互作用。这个循环系统使他们能够研究基于可溶性因子在培养的3T3 L1脂肪细胞和INS1β细胞之间的运输。研究发现，在高葡萄糖和胰岛素条件下进行流动培养会增加培养基中脂肪细胞来源的IL-6、TNF-α和脂联素的分泌水平。反过来，脂肪细胞来源的IL-6会增强同一培养基中β细胞的胰岛素分泌，从而建立一个前馈回路。这种机制可能导致肥胖相关T2D的高胰岛素血症和促炎状态。这些发现突出了流动微流控技术在模拟肥胖中脂肪细胞与β细胞相互作用方面的优势，为肥胖相关β细胞功能障碍提供了新的见解。
