Hormones, known for their combination of childbirth and society, reveal a hidden talent: controlling blood sugar through previously unknown pathways of the pancreas.
Scientists at Fukushima Medical University have found that oxytocin triggers insulin production not by directly targeting insulin-producing cells but by activating a group of hormones that release a powerful diabetes drug called GLP-1.
This discovery could reshape our understanding of how the body manages glucose naturally and could lead to new diabetes treatments that are more like the body’s own control system.
Unexpected cellular route
A team led by Kasumi Hattori and corresponding authors Kenju Shimomura and Yuko Maejima made a discovery while studying the conflicting reports on the effects of oxytocin on blood sugar. Previous studies have shown mixed results – some have found that oxytocin raises blood sugar, while others lowers it.
The researchers solved the puzzle using mice with or without functional oxytocin receptors. They found that oxytocin caused an initial peak of blood sugar regardless of whether the receptor was effective, but only mice with functional receptors showed a crucial follow-up: increased insulin production.
“WT mice showed a significant increase in insulin levels at 15 minutes, while OXTR KO mice did not,” the researchers reported.
GLP-1 connection
The breakthrough came true when researchers discovered exactly how oxytocin boosted insulin. Oxytocin does not act directly on the beta cells that produce insulin, but mainly targets alpha cells, and pancreatic cells are usually responsible for making pancreatic thrombocytosis, a hormone that raises blood sugar.
The team found that these alpha cells can produce their own version of GLP-1, the same hormone that revolutionized diabetes treatment in drugs like Ozempic and Wegovy. This “ISLET GLP-1” works locally within the pancreas to stimulate insulin release from nearby beta cells.
What makes this discovery particularly interesting is the timing and conditions required. When blood sugar levels are high, oxytocin only triggers a significant increase insulin – when the body needs more insulin, oxytocin contributes to a significant increase insulin. Under normal glucose conditions, hormones have little effect.
Natural safety switch
This glucose-dependent effect represents a built-in safety mechanism that current diabetes drugs attempt to mimic. Unlike some diabetes medications that can cause dangerous hypoglycemia, this natural pathway is activated only when glucose levels rise.
The researchers found that compared with insulin-producing beta cells, about 95% of glucagon-producing alpha cells have oxytocin receptors, with significantly higher receptor concentrations. This distribution pattern suggests that the alpha-cell pathway may be the main pathway affecting blood sugar control.
Beyond News
Although the basic findings have attracted attention, the study reveals other key details about time and cellular mechanics. Studies have shown that the effect of oxytocin unfolds at different stages: even without direct glucose peaks (within 15 minutes) of functional receptors, followed by receptor-dependent insulin release, thereby reducing glucose levels.
The team also found that although oxytocin is strongly present in glucagon-producing cells, the pathway does not affect glucagon secretion itself. This selectivity suggests that hormones specifically redirect these cells to GLP-1 production rather than altering its main glucagon function.
Effects on diabetes treatment
“Although the detailed mechanisms that stimulate GLP-1 secretion in ISLEL are still to be elucidated and to the best of our knowledge our study requires further research, our current study is the first to report the effect of OXT on inducing ISLES ISLET GLP-1 secretion,” the researchers noted.
This discovery opens up new possibilities for diabetes therapy to work by enhancing the body’s natural oxygenated protein GLP-1 pathway. Future treatments are not to inject the synthetic GLP-1 analogue, but to stimulate the pancreas to produce its own GLP-1 in response to oxytocin-like compounds.
This approach may be particularly valuable for older people with diabetes, providing a more natural way to restore glucose control, as the body produces insulin naturally decreases naturally with age.
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