A disordered thermostat  pg. 5

In vivo imaging

The secret life of the beta cell is being revealed. Thanks to recent advances in laser microscopy, scientists are able to study the “behavior” of beta cells in pancreatic islets grown in the laboratory, and even in animals.

At Vanderbilt, for example, David W. Piston, Ph.D., has helped pioneer the use of fluorescence imaging methods to trace the sequence of events, beginning with the entry of glucose into beta cells, that ultimately leads to insulin secretion.

A goal is to figure out why, in type 2 diabetes, beta cells are unable to respond normally to blood glucose, and what might be done to “fix” that problem. “It’s hard to learn these things without looking in the intact animal,” says Piston, professor of Molecular Physiology & Biophysics and Physics.

David Piston, Ph.D., demonstrates two-photon excitation microscopy, a technique he has pioneered to study the sequence of intracellular events leading to insulin secretion, and what may go wrong in diabetes. “We know so little,” he says. “It’s going to take a long time and a lot of very insightful experiments to really dissect this out.”
Photo by Anne Rayner
The techniques, which include two-photon excitation microscopy, also enable Piston to watch mouse islets grow a new blood supply when they are transplanted into another part of the body. This information could lead to improvements in islet transplantation as a treatment for type 1 diabetes.

“Islets are really a cellular transplant as opposed to an organ transplant. They have to develop new blood vessels,” explains Alvin C. Powers, M.D., director of the Vanderbilt Diabetes Center, who is working with Piston on the project. “How do cells that are transplanted survive, and how can you improve that process?”

Whole animal studies

Many studies of how glucose is produced or used have been conducted in dogs because their blood vessels are large enough to allow detailed studies of glucose, insulin and all of the other factors that play a role in the disease.

At Vanderbilt, Masakazu Shiota, Ph.D., assistant professor of Molecular Physiology & Biophysics, has miniaturized a method for measuring insulin sensitivity in muscle so it can be applied to rats and mice, which are easier to handle. The technique enables researchers to measure how much radiolabeled glucose is absorbed by muscle in response to a continuous infusion of insulin.

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