Insulin resistance, a precursor for the development of type 2 diabetes (T2D), propagates among heterologous tissues through dysregulated lipid... Show moreInsulin resistance, a precursor for the development of type 2 diabetes (T2D), propagates among heterologous tissues through dysregulated lipid flux, as well as dysregulated glucose production, and secretion of cytokines, adipokines and hepatokines. Although T2D is characterized by systemic insulin resistance, disruption of insulin signaling in the liver and adipose tissue recapitulates many aspects of T2D, including enhance endogenous glucose production as well as defects of insulin action. Mechanistic studies often aim to provide fundamental understanding of the observations from human and animal studies. Due to the complexity of animal models and the multifactorial character of T2D, there is a strong need to develop advanced experimental systems such as in vitro models that can enable the recapitulation of the complex physiology of the in vivo system and enable investigation of the pathological pathways as well as identify novel treatment options. The overall goal of this study was to develop insulin resistant models of adipose tissue and liver to study the metabolic function of each organ as well as to the organ-organ crosstalk. To accomplish this goal, four specific aims were pursued: (1) Establish adipose tissue on-a-chip to study the metabolic function of the adipocytes in flow culture; (2) Develop towards an insulin resistant adipose on-a-chip to study the metabolic function of adipocytes in setting of insulin resistance; (3) Develop insulin resistant liver on-a-chip to investigate the metabolic function of hepatocytes in setting of insulin resistance; (4) Develop adipose-liver on-a-chip in setting of insulin resistance to identify the metabolic interaction between organs. Show less
