Low dose of serotonin-acting chemical improves blood sugar tolerance

Nov 06, 2007

An appetite-suppressing chemical also improves glucose tolerance and lowers insulin levels in obese and diabetic mice, researchers report in the November issue of Cell Metabolism, a publication of Cell Press. Importantly, the researchers found, those effects of the drug occurred at a low dose that had no influence on feeding behavior, body weight, activity level, or energy expenditure.

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.”

Source: Cell Press

Explore further: Dual role: Key cell division proteins also power up mitochondria

add to favorites email to friend print save as pdf

Related Stories

Fish exposed to SSRIs exhibit abnormal behavior, study finds

Mar 06, 2012

Fish exhibit abnormal behavior and lower levels of anxiety when exposed to Selective Serotonin Reuptake Inhibitors (SSRI), which are common drugs used to treat depression, among other disorders. The study, by Baylor University ...

Crystal structure shows how motor protein works

Sep 18, 2011

The crystal structure of the dynamin protein — one of the molecular machines that makes cells work — has been revealed, bringing insights into a class of molecules with a wide influence on health and disease.

Antidepressants linked to thicker arteries

Apr 02, 2011

Antidepressant use has been linked to thicker arteries, possibly contributing to the risk of heart disease and stroke, in a study of twin veterans. The data is being presented Tuesday, April 5 at the American College of Cardiology ...

Recommended for you

Proper stem cell function requires hydrogen sulfide

1 hour ago

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

Bionic ankle 'emulates nature'

7 hours ago

These days, Hugh Herr, an associate professor of media arts and sciences at MIT, gets about 100 emails daily from people across the world interested in his bionic limbs.

Firm targets 3D printing synthetic tissues, organs

8 hours ago

(Medical Xpress)—A University of Oxford spin-out, OxSyBio, will develop 3D printing techniques to produce tissue-like synthetic materials for wound healing and drug delivery. In the longer term the company ...

User comments : 0

More news stories

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Is Parkinson's an autoimmune disease?

The cause of neuronal death in Parkinson's disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person's own immune system, similar to the ...