Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system.

ABSTRACT: Current research on metabolic disorders and diabetes relies on animal models because multi-organ diseases cannot be well studied with standard in vitro assays. Here, we have connected cell models of key metabolic organs, the pancreas and liver, on a microfluidic chip to enable diabetes research in a human-based in vitro system. Aided by mechanistic mathematical modeling, we demonstrate that hyperglycemia and high cortisone concentration induce glucose dysregulation in the pancreas-liver microphysiological system (MPS), mimicking a diabetic phenotype seen in patients with glucocorticoid-induced diabetes. In this diseased condition, the pancreas-liver MPS displays beta-cell dysfunction, steatosis, elevated ketone-body secretion, increased glycogen storage, and upregulated gluconeogenic gene

SUBMITTER: Rigal S 

PROVIDER: S-EPMC11258270 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature