A Microphysiological Model of Progressive Human Hepatic Insulin Resistance.

ABSTRACT:

Background & aims

Hepatic insulin resistance is a fundamental phenomenon observed in both Type 2 diabetes (T2D) and metabolic (dysfunction) associated fatty liver disease (MAFLD). The relative contributions of nutrients, hyperinsulinemia, hormones, inflammation, and other cues are difficult to parse in vivo as they are convoluted by interplay between the local and systemic events. Here, we used a well-established human liver microphysiological system (MPS) to establish a physiologically-relevant insulin-responsive metabolic baseline and probe how primary human hepatocytes respond to controlled perturbations in insulin, glucose, and free fatty acids (FFAs).

Methods

Replicate liver MPS were maintained in media with either 200 pM (normal) or 800 pM (T2D) insulin for up t

SUBMITTER: Hellen DJ 

PROVIDER: S-EPMC11741310 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature