Nerve signals sent to the pancreas after eating play a critical role in blood su

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Nerve signals sent to the pancreas after eating play a critical role

in blood sugar control

http://www.news-medical.net/?id=18310

Nerve signals relayed directly to the pancreas after eating a meal

play a critical role in normal blood sugar control, according to a

report in Cell Metabolism. Therefore, drugs that increase the

sensitivity to such signals might offer a new approach to diabetes

treatment, the researchers said.

Mice in which the pancreas cells that produce insulin, or beta cells,

lack so-called M3 muscarinic acetylcholine receptors develop some

symptoms of diabetes, including impaired glucose tolerance and

reduced insulin release, the authors report. M3 receptors are

normally on the receiving end of messages relayed by involuntary

nerves that indicate the presence of food.

In contrast, mice genetically altered to harbor an excess number of

beta cell M3 receptors show the opposite: a profound increase in

glucose tolerance and insulin release, the researchers found.

Moreover, such animals become resistant to developing symptoms of

diabetes or prediabetes when fed a high-fat diet.

The findings suggest that drugs that boost the activity of the M3

receptors on pancreatic beta cells might have therapeutic potential,

said Jurgen Wess of the National Institute of Diabetes and Digestive

and Kidney Diseases.

" There may be ways to specifically drive up the number of M3

receptors expressed in pancreatic beta cells, " Wess said. " It might

also be possible to enhance M3 receptor signaling in beta cells by

targeting proteins that modulate M3 receptor function in a specific

fashion. "

Receptors of the same type are also found in other parts of the body,

he explained. Therefore, drugs that directly stimulate M3 receptors

in general would likely come with problematic side effects--for

example, causing smooth muscles to contract.

One of three branches of the involuntary nervous system, the

parasympathetic, or " rest and digest " system fulfills many roles--

slowing the heart rate, dilating blood vessels, and stimulating

digestive secretions.

Food intake is known to trigger an increase in parasympathetic nerve

impulses involving signals of different origins that are integrated

in the brain, the researchers said. In the pancreas, parasympathetic

nerve endings release the messenger acetylcholine before and most

likely after food is absorbed.

" However, the importance of parasympathetic innervation of pancreatic

beta cells in maintaining normal glucose balance had remained

controversial, " Wess said. " Much of this controversy has arisen

because peripheral parasympathetic nerves release at least five

different neurotransmitters, and increased parasympathetic outflow

affects the function of many organs and tissues that have important

metabolic functions. "

The researchers overcame those difficulties in the current study by

examining the glucose tolerance and insulin release of otherwise

normal mice that were deficient for M3 receptors only in pancreatic

beta cells, and in mice that contained an increased number of M3

receptors specifically in beta cells.

" We've established an important role for the native M3 receptor in

beta cells in maintaining normal insulin release and blood glucose

levels, " Wess said. " It's also clear from our findings that the

parasympathetic nervous system's modulation of blood sugar is not a

transient event--its effects on the pancreas are sustained for a long

time after a meal. "

http://www.cellmetabolism.org