"We were surprised to find that the Snapin-on mice didn't have more or bigger pancreas cells, they just made more insulin naturally," says Hussain. "This means all our insulin-secreting cells have this amazing reserve of insulin that we didn't really know existed and a switch that controls it."
To see if permanently turning off Snapin would reduce insulin release and further demonstrate that Snapin controls the process, the researchers first grew normal mouse pancreas cells in a dish, and treated them with a chemical that stopped them from making the Snapin protein. They again bathed the cells in glucose and measured how much insulin was released by the cells. Normal cells released 5.8 billionths of a gram of insulin, whereas cells with no Snapin only released 1.1 billionths of a gram of insulin about 80 percent less.
"These results convinced us that Snapin is indeed the switch that releases insulin from the pancreas," says Hussain.
Normally, according to Hussain, when we ingest glucose, the pancreatic beta cells release an initial burst of insulin almost immediately, then gradually release more insulin about 15 minutes later. However, people with type 2 diabetes and mice engineered to react metabolically like people with type 2 diabetes don't release this initial spurt of insulin when fed glucose, but still have the later gradual insulin release.
"We knew how important the first burst of insulin is for controlling our blood sugar, but we did not know what really went wrong in our beta cells in people with type 2 diabetes," says Hussain. "We have drugs that restore the first burst of insulin and yet we did not completely understand how they work."
Hussain then questioned whether Snapin could be used to fix the defects in cells from a diabetic animal.
Since the cells with Snapin on made too much insulin, researchers wanted to see if
|Contact: Vanessa McMains|
Johns Hopkins Medical Institutions