An explosion of new research is vastly changing scientists' understanding of diabetes and giving new clues about how to attack it.

The fifth leading killer of Americans, with 73,000 deaths a year, diabetes is a disease in which the body's failure to regulate glucose, or blood sugar, can lead to serious and even fatal complications. Until very recently, the regulation of glucose — how much sugar is present in a person's blood, how much is taken up by cells for fuel and how much is released from energy stores — was regarded as a conversation among a few key players: the pancreas, the liver, muscle and fat.

Now, however, the "party" is proving to be much more complex than anyone had shown before.

New research suggests that a hormone from the skeleton, of all places, may influence how the body handles sugar.

Last summer, researchers at Columbia University Medical Center published startling results showing that a hormone released from bone may help regulate blood glucose.

When the lead researcher, Dr. Gerard Karsenty, first described the findings at a conference, the assembled scientists "were overwhelmed by the potential implications," said Dr. Saul Malozowski, senior adviser for endocrine physiology research at the National Institute of Diabetes and Digestive and Kidney Diseases, who was not involved in the research. "It was coming from left field. People thought, 'Oof, this is really new.'

"For the first time," he went on, "we see that the skeleton is actually an endocrine organ," producing hormones that act outside of bone.

In previous work, 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.

Mounting evidence also demonstrates that signals from the immune system, the brain and the gut play critical roles in controlling glucose and lipid metabolism. (The findings are mainly relevant to Type 2 diabetes, the more common kind, which comes on in adulthood.)

Focusing on the cross-talk among more different organs, cells and molecules represents a "very important change in our paradigm" for understanding how the body handles glucose, said Dr. C. Ronald Kahn, a diabetes researcher and professor at Harvard Medical School.

The defining feature of diabetes is elevated blood sugar. But the reasons for abnormal sugar seem to "differ tremendously from person to person," said Dr. Robert A. Rizza, a professor at the Mayo Clinic College of Medicine. Understanding exactly what signals are involved, he said, raises the hope of "providing the right care for each person each day, rather than giving everyone the same drug."