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Insulin-producing cells found in unexpected places

by Ruth SoRelle, MPH

Lawrence Chan, MD

More than a year ago, when Lawrence Chan, MD, and his laboratory colleagues at Baylor College of Medicine in Houston were working with gene therapy to cure diabetes in mice, they found something interesting. Insulin-producing cells normally found only in the pancreas and thymus had appeared in other organs. They appeared before the gene therapy occurred.

“There were only a few,” said Chan, BCM professor of medicine and molecular and cellular biology as well as chief of the division of diabetes, endocrinology and metabolism. “We thought it must be an artifact or contamination. I said, ‘Do it again.’”

The researchers led by Hideto Kojima, PhD, did it again. Eventually, the care they used and the precision of their measurements convinced Chan that they were right. Insulin-producing cells were cropping up in diabetic mice and only those mice.

Finding the unexpected

“We started sectioning every organ,” said Chan. “We found it in the fat cells, the bone marrow cells as well as the spleen and thymus.”

Finding the insulin-producing cells in the thymus was no surprise. The thymus produces many proteins – among them insulin.

“It is thought that you produce antigens (such as insulin) in the thymus (an organ important in the immune system) so you become tolerant of it and do not attack the insulin your own body makes,” he said.

Finding the beta or insulin-producing cells in the liver, fat and bone was unexpected, however.

Chan and his colleagues began to look for some outside cause. In some mice, they caused diabetes with a chemical toxin. They wondered if this might have a toxic effect that caused the insulin-producing cells.

They used a mouse that was bred to have diabetes because of the loss of a biological chemical called leptin.

“We saw the same things in these mice,” he said.

When mice are fed a high-fat diet, they become diabetic. These mice had the insulin-producing cells as well.

The mice that lacked leptin and those who developed diabetes on a high fat diet suffered from insulin resistance, a form of diabetes similar to type 2 diabetes in people. The mice that had been treated with the chemical toxin had an insulin deficiency. Yet both kinds of mice had the odd insulin-producing cells cropping up in odd organs and tissues.

High blood sugar

“The common denominator is high blood sugar – not lack of insulin or insulin resistance,” said Chan.

One of his colleagues then did an experiment in which he injected glucose into mice every two hours. He checked the animals for the appearance of the insulin-producing cells after three and then 15 days. In all the animals, he found the cells within three days of beginning the treatment.

“High blood sugar causes these animals to produce insulin,” said Chan.

Where do the cells originate? Chan said they arise from the same tissues that spawn many of the body’s cells – the bone marrow.

“The number of cells is small as is the amount of insulin produced,” said Chan. “It doesn’t do anything to correct their disease. What is the significance?”

It is important to remember that there are two types of diabetes. Type 2 diabetes, the more common type that usually occurs in adults, reflects the cell’s inability to take in and metabolize glucose. Type 1 diabetes is an autoimmune disease in which the body produces antibodies to both the beta cells and insulin. The insulin-producing cells in the various organs and tissues occur in both types of diabetes.

Autoimmunity in type 1 diabetes

“In type 1 diabetes, you have autoimmunity to insulin,” said Chan. That means the person develops antibodies that attack insulin and the cells that make it.

“You also increase the number of insulin-producing cells in the thymus. And there are insulin-producing cells in the other tissues as well. The question is, ‘what does that do?’"

In the mother’s womb, when a developing baby is exposed to high blood sugar, the baby produces more insulin in the thymus.

“That could protect the baby,” said Chan. “What about expression of insulin-producing cells in the liver, adipose (fat) or bone marrow? What would that do to insulin autoimmunity? Could it have an effect – either bad or good? We don’t know.”

Discovering the reasons for those cells and the effect of the minuscule amounts of insulin they produce could have important implications for future treatment of diabetes, said Chan.

If this inherent property of cells can be harnessed and augmented, Chan speculates, scientists could use it to generate insulin-producing cells from other tissues for the treatment of diabetes. If the production of insulin by cells outside the pancreas affects the immune system, which goes awry in people predisposed to type 1 diabetes, it could affect the course of the disease.

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