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 between a few key players: the pancreas, the liver, muscle and fat.

Now, however, the party is proving to be much louder and 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. 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 between 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.