Chemical genetic-based phenotypic screen reveals novel regulators of gluconeogenesis in human primary hepatocytes.

ABSTRACT: Insulin resistance is a pathophysiological hallmark of type 2 diabetes and nonalcoholic fatty liver disease. Under the condition of fat accumulation in the liver, suppression of hepatic glucose production by insulin is diminished. In order to gain deeper understanding of dysregulation of glucose production in metabolic diseases, in the present study, we performed an unbiased phenotypic screening in primary human hepatocytes to discover novel mechanisms that regulate gluconeogenesis in the presence of insulin. To optimize phenotypic screening process, we used a chemical genetic screening approach by building a small-molecule library with prior knowledge of activity-based protein profiling. The "positive hits" result from the screen will be small molecules with known protein targets. This ma

SUBMITTER: Zou H 

PROVIDER: S-EPMC6093908 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature