The complex landscape of diabetes

An Amanda Schaffer article, "In Diabetes, a Complex of Causes" in the Science Times covers recent research on Type 2 diabetes. The interesting part of the research is the extent that insulin resistance and related hormonal signaling have been linked to processes ranging from inflammation, bone metabolism, and the brain:

In previous work, Dr. Karsenty had shown that leptin, a hormone produced by fat, is an important regulator of bone metabolism. In this work, he tested the idea that the conversation was a two-way street. "We hypothesized that if fat regulates bone, bone in essence must regulate fat," he said.
Working with mice, he found that a previously known substance called osteocalcin, which is produced by bone, acted by signaling fat cells as well as the pancreas. The net effect is to improve how mice secrete and handle insulin, the hormone that helps the body move glucose from the bloodstream into cells of the muscle and liver, where it can be used for energy or stored for future use. Insulin is also important in regulating lipids.

The common theme seems to be this: Once, doctors focused on easy-to-measure biomarkers, like blood glucose level. But these are in turn affected by many different physiological processes -- far from the pancreas --- many in feedback relations regulated by multiple signaling molecules.

The brain in particular exerts a powerful drain on blood glucose. So you might expect something like this:

"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 inadequate amounts, he continued, 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."

There's a lot more, although the article doesn't touch on the recent genomic scans for diabetes-related genes.