In yesterday’s post, Diabetes: A ‘Complex of Causes’, I wrote about exciting new research reported by the New York Times implicating a causal relationship between the skeletal and immune systems to type 2 diabetes. Other studies also show a connection between blood sugar regulation to the brain and intestines.
Over a hundred years ago, Claude Bernard (a French physiologist) hypothesized that the brain was an integral part in blood sugar metabolism. He experimented on animals by punturing their brains in key areas, managing to disrupt their blood sugar regulation. In essence, he made the animals become diabetic.
Dr. C. Ronald Kahn, a diabetes researcher and professor at Harvard Medical School, said that virtually no one followed up on this finding. And, although people thought about glucose as a critical fuel for the brain, they did not investigate the brain’s role in glucose regulation. Only in modern times has this possible link been explored further due to advances in laboratory techniques such as genetic research.
All in Your Head
In 2000, Dr. Kahn’s experiments to manipulate mice’s insulin receptors have demonstrated that, without those specialized cells in the brain, the mice were incapable of regulating glucose and eventually developed diabetes.
Several new studies indicate that recent papers suggest that – in mice – glucose sends signals directly to neurons in the hypothalamus (the part of brain responsible for regulating appetite, temperature and libido). These signals are critical in the mice for normal blood sugar metabolism.
(Except from the October 16th NY Times article)
“If the brain is getting the message that you have adequate amounts of these hormones and nutrients, it will constrain glucose production by the liver and keep blood glucose relatively low,” said Dr. Michael W. Schwartz, a professor at the University of Washington. But if the brain senses insufficient amounts, he goes on, it will “activate responses that cause the liver to make more glucose, and new evidence suggests that this contributes to diabetes and impaired glucose metabolism.”
The brain, therefore, appears to be listening to — and weighing and making sense of — a chorus of signals from insulin, leptin, free fatty acids and glucose itself. In response, it appears to send signals to liver and muscle cells by way of several nerves, though additional mechanisms are probably involved.
A Gut Feeling
“Food comes in through the gut, so of course you should look there” for molecules involved in glucose regulation, said Dr. Rizza. “But few people realized this until very recently.”
Incretins, or hormones secreted by the small intestine, apparently directly signal the pancreas and brain and cause blood sugar levels to decrease. With this reduction in blood sugar, animals and people have been shown to eat less and lose weight.
New clinical trials are studying molecules that either inhibit incretins from degrading in the body or can mimic the effects of the hormone. The FDA has approved two drugs thus far, but side effects are still to be determined.
“The picture is becoming more and more complicated,” said Dr. Alan R. Saltiel, director of the Life Sciences Institute at the University of Michigan. “And let’s face it, it was pretty complicated before.”