Project Grant R56DK141542

Albert Einstein College of Medicine received a $252,000 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective April 1, 2026 through March 31, 2027. The award supports investigator-initiated biomedical research examining the metabolic function of a novel subset of periportal hepatocytes, termed dual-modal hepatocytes, which simultaneously express both gluconeogenic and lipogenic genes in the fed state. This research investigates how these hepatocytes remain gluconeogenic despite insulin suppression and explores the potential mechanisms underlying hepatic insulin resistance through the expansion or proliferation of this unique hepatocyte population, rather than through acquired cellular insulin resistance.

The research deliverables include basic and clinical biomedical investigations into the temporal and spatial regulation of gluconeogenesis within the liver's hexagonal lobular architecture, with particular focus on understanding the distinct metabolic properties and gene expression patterns of hepatocytes across the periportal-to-pericentral axis. Findings from this project are expected to advance understanding of liver disease pathogenesis and metabolic dysfunction, contributing to improved prevention and treatment strategies for diabetes and related metabolic disorders that align with NIDDK's research priorities.