Project Grant R01DK142926

Award Summary

Weill Medical College of Cornell University received a $770,603 Project Grant 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 March 1, 2026, through February 28, 2031. The research focuses on elucidating GIP (glucose-dependent insulinotropic polypeptide) receptor signaling mechanisms through investigation of a human genetic variant (GIPR-Q354) linked to reduced weight and altered glucose metabolism. The research project utilizes engineered mouse models expressing this GIP receptor variant to molecularly dissect how incretin hormones regulate insulin secretion and glucose tolerance at both acute and developmental levels.

The primary product of this award is fundamental scientific research advancing understanding of incretin hormone biology and GIP receptor function. By characterizing the molecular mechanisms underlying the GIPR-Q variant—including its increased accumulation in the trans-Golgi network and enhanced beta-arrestin2 binding—this research provides critical insights into how genetic variations influence metabolic regulation. These findings have direct clinical relevance, as they inform the therapeutic application and optimization of incretin-based therapies currently used in diabetes and metabolic disease treatment, while simultaneously exploring their potential applications in cancer and neurodegenerative disease treatment.