The decades-old drug compound, known as m-chlorophenylpiperazine (mCPP), triggers serotonin receptors in the brain. The findings suggest a new strategy for treating the rising tide of people with type 2 diabetes via targeting the so-called serotonin 2C (5-HT2C) receptors.
“Though just a first step, this work provides a new direction in the search for novel pathways and molecules in the brain to target for the treatment of type 2 diabetes,” said Lora Heisler of the University of Cambridge. “The challenge now is to come up with drugs that selectively target 5-HT2C receptors safely and effectively.”
mCPP has primarily been used in scientific studies of the serotonin pathway and may not itself be appropriate for type 2 diabetes treatment due to its other known effects, Heisler added. Heisler’s collaborators included Joel Elmquist of the University of Texas Southwestern Medical Center and Andrew Butler of Louisiana State University System.
Serotonin is a chemical nerve messenger with effects on physiology and behavior, including mood, sleep, and appetite, that are mediated by multiple serotonin receptors clustered into seven distinct families that are widely expressed in the central and/or peripheral nervous systems, the researchers explained. Earlier studies had explored serotonin-acting drugs in treating obesity, but the possibility of a direct role for serotonin in the development and treatment of type 2 diabetes has received little attention, they said.
Earlier studies revealed that mice lacking the 5-HT2C receptor develop insulin resistance and type 2 diabetes and later overeat and become obese. In the current study, the researchers examined whether a drug that acts on 5-HT2C receptors could improve glucose tolerance. They show in mouse models of obesity and insulin resistance that the drug does improve blood sugar levels. Moreover, it does so even at concentrations that do not lead to reductions in food intake or body weight.
The researchers further report evidence that the serotonin-acting drug may work by stimulating “a-melanocyte-stimulating hormone” (a-MSH) in the brain’s arcuate nucleus, a portion of the hypothalamus important for appetite control. They show that the primary effect of the drug on glucose balance requires activation of one type of a-MSH receptor, called melanocortin-4 receptors (MC4R).
“Our findings add to emerging evidence that the brain may have important influences on glucose metabolism and insulin action,” Heisler added.
While the findings do link serotonin pathways to improved blood sugar tolerance, serotonin supplements would not produce this effect, Heisler noted. That’s because serotonin taken in through the diet cannot cross the blood-brain barrier to reach the critical receptors.
“The identification of new classes of antidiabetic agents is a clinical imperative,” the researchers concluded. “The findings presented here identify a novel therapeutic application for a class of pharmacological compounds developed more than two decades ago. We demonstrate that 5-HT2C receptor agonists significantly improve glucose tolerance and [lower insulin levels in mouse] models of obesity and type 2 diabetes via an MC4R-dependent mechanism. These findings not only delineate specific neuronal pathways of relevance to a highly prevalent metabolic disease but also suggest that 5-HT2C receptor agonists may prove an effective and mechanistically novel treatment for type 2 diabetes.”
Cathleen Genova | alfa
Exciting Plant Vacuoles
14.06.2019 | Julius-Maximilians-Universität Würzburg
A microscopic topographic map of cellular function
13.06.2019 | University of Missouri-Columbia
Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.
Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...
Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.
The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...
Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.
The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....
Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.
Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...
Fraunhofer IZM is joining the EUROPRACTICE IC Service platform. Together, the partners are making fan-out wafer level packaging (FOWLP) for electronic devices available and affordable even in small batches – and thus of interest to research institutes, universities, and SMEs. Costs can be significantly reduced by up to ten customers implementing individual fan-out wafer level packaging for their ICs or other components on a multi-project wafer. The target group includes any organization that does not produce in large quantities, but requires prototypes.
Research always means trying things out and daring to do new things. Research institutes, universities, and SMEs do not produce in large batches, but rather...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
14.06.2019 | Information Technology
14.06.2019 | Materials Sciences
14.06.2019 | Medical Engineering