Glucagon-like peptide-1 (GLP-1) is a molecule with relevance in contemporary medicine. Its discovery and understanding have reshaped approaches to various health conditions. This naturally occurring substance has garnered attention for its wide-ranging effects.
What is GLP-1?
GLP-1 is a hormone produced primarily in the L-cells of the small intestine. It is released into the bloodstream in response to food intake, with concentrations increasing two to three-fold after a meal. It plays a role in the body’s natural regulation of glucose and appetite.
Once released, GLP-1 stimulates the pancreas to secrete insulin in a glucose-dependent manner, meaning it only prompts insulin release when blood sugar levels are elevated. It also lowers blood sugar by inhibiting the secretion of glucagon, a hormone that raises blood glucose. GLP-1 slows down gastric emptying, which reduces the rate at which glucose enters the bloodstream after eating, and acts on appetite centers in the brain to promote feelings of fullness, thereby reducing food intake.
The Pioneers of GLP-1 Discovery
The journey to understanding GLP-1 began in the 1970s with researchers like Dr. Joel Habener and Dr. Jens Juul Holst. Their early investigations focused on glucagon-like peptides, exploring hormones secreted during digestion. This foundational work laid the groundwork for identifying GLP-1’s biological potency.
Dr. Joel Habener, then at Massachusetts General Hospital and Harvard Medical School, worked on identifying prohormones for pancreatic hormones like glucagon. In the 1980s, his laboratory’s gene cloning efforts revealed that the gene encoding glucagon also contained sequences for related hormones, which were later identified as GLP-1 and GLP-2. Simultaneously, Dr. Svetlana Mojsov, a chemist in the same institution, independently identified the active portion of GLP-1, known as GLP-1(7-37). She was instrumental in producing large quantities of the peptide and developing antibodies to detect it.
Across the Atlantic, Dr. Jens Juul Holst at the University of Copenhagen was observing that patients undergoing intestinal surgery experienced elevated insulin levels and reduced blood sugar. He attributed these changes to gut-related hormones, including glucagon. Holst and his colleagues isolated GLP-1 from pigs and confirmed its ability to increase pancreatic insulin secretion. The collaborative efforts of Habener, Mojsov, and Holst, along with Dr. Daniel Drucker, led to scientific papers describing GLP-1’s active form in rat guts and its correlation with increased insulin levels, culminating in its characterization by 1988.
From Discovery to Therapeutic Breakthroughs
The understanding of GLP-1’s physiological actions led to the development of a class of medications known as GLP-1 receptor agonists. These drugs mimic the effects of natural GLP-1 in the body. They stimulate insulin release, inhibit glucagon secretion, slow gastric emptying, and reduce appetite, making them effective for managing blood sugar levels and promoting weight loss.
The first GLP-1 receptor agonists gained approval as treatments for type 2 diabetes starting in the 2000s. Later, some of these medications were also approved for long-term weight management, addressing obesity. These therapeutic agents represent a direct application of the scientific discoveries made decades earlier, showcasing how unraveling the mechanisms of natural hormones can lead to advancements in medical treatment.