CP v2

Tag: Hypothalamus

  • Scientists pinpoint metformin’s brain pathway, offering new clues for targeted type 2 diabetes treatment

    Scientists pinpoint metformin’s brain pathway, offering new clues for targeted type 2 diabetes treatment

    After more than 60 years as a first-line drug for type 2 diabetes, metformin is yielding a clearer explanation for how it lowers blood sugar. Researchers report that part of its glucose-lowering effect depends on a specific brain circuit, not only the liver or the gut.

    The study, led by Baylor College of Medicine and international collaborators, was published in Science Advances. It focuses on the ventromedial hypothalamus, a brain region known to help regulate whole-body metabolism.

    A protein switch in the hypothalamus

    The team centered on Rap1, a small signaling protein active in the ventromedial hypothalamus. They found that clinically relevant metformin dosing relied on suppressing Rap1 activity in this brain area to reduce blood glucose.

    To test the mechanism, the researchers used mice engineered to lack Rap1 in the ventromedial hypothalamus and then fed them a high-fat diet to model diabetes. In those mice, low-dose metformin did not improve blood sugar, while insulin and GLP-1–based drugs still worked.

    Why tiny brain doses mattered

    In another experiment, researchers delivered extremely small amounts of metformin directly into the brains of diabetic mice. Even at doses thousands of times lower than typical oral exposure, blood glucose fell markedly, supporting a central nervous system effect.

    The study also identified SF1 neurons in the ventromedial hypothalamus as key responders, becoming activated when metformin reached the brain. Electrophysiology data suggested metformin increased activity in most of these neurons, but only when Rap1 signaling was intact.

    What it could mean next

    The findings add to a growing view that metformin’s benefits may come from multiple organs working together, with the brain reacting at comparatively low drug levels. The authors argue that mapping this pathway could help guide future diabetes therapies that more precisely target glucose control.

    The researchers also pointed to broader interest in metformin’s neurological effects, including ongoing questions about brain aging. They plan to examine whether the same Rap1-linked signaling helps explain other observed effects of the drug beyond diabetes.

  • Researchers map a brain pathway that may signal fullness: Astrocytes emerge as a new appetite control target

    Researchers map a brain pathway that may signal fullness: Astrocytes emerge as a new appetite control target

    Scientists have identified a previously underappreciated brain signaling pathway that helps the body recognize when it is time to stop eating, shifting attention from neurons alone to a broader cellular network. The work, published April 6, 2026 in Proceedings of the National Academy of Sciences, focuses on how the hypothalamus processes post-meal fuel signals.

    The study centers on astrocytes, abundant brain cells long viewed mainly as support for neurons, and suggests they can actively shape appetite control. Researchers say this mechanism could eventually inform new strategies for obesity and eating-disorder treatments, though the findings are based on animal experiments.

    How glucose signals reach the brain

    After a meal, glucose levels rise and are sensed in part by tanycytes, specialized cells that line fluid-filled spaces in the brain. In the experiments, tanycytes responded to glucose by producing lactate, a metabolic byproduct that can function as a signaling molecule in the surrounding tissue.

    For years, lactate was often discussed as a signal that could act directly on appetite-regulating neurons. This research argues the message commonly takes an additional step, with astrocytes serving as a crucial intermediary before neurons that promote satiety are engaged.

    Astrocytes as appetite messengers

    The team found that astrocytes detect lactate via a receptor known as HCAR1 and, once activated, can release glutamate to influence nearby neurons. In this model, that astrocyte-to-neuron signal increases the excitability of POMC neurons, a population associated with suppressing appetite.

    In closely observed lab tests, stimulating glucose handling in a single tanycyte led to broader astrocyte activity nearby, suggesting the signal can spread through a local network. The researchers also described evidence consistent with a dual effect in the hypothalamus, potentially supporting satiety pathways while dampening hunger-promoting activity through separate routes.

    What this means for obesity research

    Because tanycytes and astrocytes exist across mammals, the authors argue the same kind of circuitry could plausibly operate in humans, but that remains to be confirmed. The next step, they say, is testing whether changing HCAR1 activity in astrocytes can reliably alter eating behavior.

    No approved drugs currently target this exact astrocyte pathway, and translating such findings into therapies typically requires years of follow-up work. Still, the researchers suggest that aiming at astrocyte signaling could one day complement existing anti-obesity approaches rather than replace them.

    The project reflects a long-running collaboration between the University of Concepción in Chile and the University of Maryland. The authors report the work was supported by Chilean research funding programs and the U.S. National Institutes of Health.