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
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology