Jens Juul Holst

The Work:

The independent and collaborative work of Daniel Drucker, Joel Habener and Jens Holst enhanced our understanding of how our gastrointestinal organs function and created new classes of drugs for the treatment of metabolic disorders, specifically type 2 diabetes, obesity and short bowel syndrome.

Drucker, Habener and Holst discovered hormones called glucagon-like peptides (GLP-1 and -2) which control the levels of Insulin and glucagon which work together to maintain healthy sugar levels. They elucidated their biology and physiological function and played critical roles in the design and testing of therapies informed by their initial and subsequent discoveries

These three scientists are awarded for a combined body of work with significant impact on the field of diabetes and short bowel syndrome but are also recognized for their individual discoveries that underpin the translational results.

In the 1970s, Holst recorded intestinal surgery patients experiencing insulin spikes and drops in blood sugar after meals, leading him to conclude that an incretin, subsequently identified as
GLP-1, along with insulin and glucagon was responsible for the glucose-induced gastrointestinal stimulation of insulin secretion that caused the changes in blood sugar levels.

Around the same time, Habener used pancreatic cells from anglerfish to demonstrate that glucagon and somatostatin were encoded in the pancreatic cells as larger, precursor hormones. During additional mammal studies he discovered two new hormones related to glucagon which are known as GLP-1 and GLP-2.

Drucker, a fellow in Habener’s lab in the 1980s, outlined the processing of proglucagon and the biology of GLP-1 action on insulin-producing cells, which led to the development of multiple types of treatments for type 2 diabetes. Together with Holst, working mostly in people, they showed that when food is ingested, GLP-1 is released into the bloodstream from cells in the gut increasing insulin release and suppressing glucagon.

Work from their labs and others led to the development of novel therapeutics to control insulin secretion in Type 2 diabetes based on understanding the action of GLP1 and its metabolism by the enzyme, DPP4, leading directly to the development of the DPP-4 inhibitors for diabetes therapy.

Drucker discovered the first actions of GLP-2 as a gut growth factor and both Drucker and Holst extensively characterized its mechanisms of action in animals and humans. The first GLP-2 analogue (teduglutide) was approved for clinical use in the treatment of short bowel syndrome in 2012.

The Impact:

Together, Drucker, Habener and Holst made major contributions to endocrinology and changed the treatment of metabolic and gastrointestinal diseases. Their work is both basic and translational, a true example of bench to bedside research.

GLP-1 therapies have been effective in the treatment of type 2 diabetes and more recently, as a treatment of obesity to reduce appetite. Drucker and Holst’s research on the function of GLP-2 and its role as an intestinal growth factor helped develop treatments for short bowel disease, decreasing the need for feeding tubes to provide nutrition in children and adults with the condition.

To date, over 100 million people with type 2 diabetes have been treated with a GLP-1 analogue or a DPP-4 inhibitor.