Porte to give Distinguished Scientist Lecture on diabetes and obesity

Major medical advances answer fundamental questions, and in so doing open new avenues for investigators to pursue. Such was the case over 30 years ago in the field of endocrinology when investigators began probing the relationship between diabetes and obesity.

Porte

Clinical studies showed that adult diabetics were often obese. What was the connection? Did obesity cause diabetes, or was it the other way around? In 1968, Dr. Daniel Porte, then an assistant professor of medicine at the UW, published an article in the American Journal of Clinical Nutrition in which he tackled these questions.

Porte reported that although obese people were at risk for developing diabetes, their blood-sugar levels were not necessarily higher than normal. In other words, hyperglycemia, or high blood-sugar levels — the classic symptom of diabetes — appeared to be triggered by something else. This other trigger continues to baffle researchers and spawn original research. It is the mechanism for abnormal insulin secretion.

Porte, now UW professor emeritus of medicine, is this year’s Distinguished Scientist for the Science in Medicine Lecture Series. He will discuss his early work, as well as the latest developments in the field, in a lecture titled “Obesity and Diabetes Mellitus: The B-Cell Connection,” from 12:15 to 1:15 p.m. on Thursday, May 18, in room T-625 of the Health Sciences Center.

Insulin, a hormone that helps us metabolize sugar, is produced by Beta cells in the pancreas. If a person’s B-cells are damaged, perhaps due to a genetic susceptibility to injury, the person becomes hyperglycemic and requires insulin to survive. This is called insulin-dependent diabetes, or Type 1.

Interestingly, however, no one is born with diabetes. There may be hereditary risk factors, Porte said, but the most common form of the disease develops in adults. This form, adult-onset diabetes, or Type 2 diabetes, is not caused by an inability to produce insulin, but by a combination of mechanisms that prevent the hormone from acting and being secreted as it should.

When a person’s insulin is ineffective at metabolizing sugar, he or she is said to be “insulin-resistant.” For years, researchers believed this was the connection between obesity and diabetes. But further studies revealed the troubling fact that most obese people were insulin-resistant, yet never developed diabetes.

Quick inroads were made when researchers began studying the nervous system and how it regulates insulin secretion. Porte and his colleagues developed the hypothesis that insulin is a signal back to the brain to regulate feeding and obesity by controlling chemicals called neuropeptides in the hypothalamus. In studies, the researchers showed that when insulin is infused into the brain, it suppresses feeding and weight. Insulin was shown to inhibit a peptide that stimulates food-intake. Thus, when food is eaten and insulin is secreted, it is taken up into the hypothalamus and suppresses food-intake to maintain a constant weight.

“There are many such signaling systems in the brain that we now know participate in this body-weight regulating system,” Porte said.

The connection between obesity and diabetes may be a mistake in this signaling system. A genetic defect in the brain’s peptides, for instance, may cause some people to have lower or higher than normal weight. Porte suggests that a person with a defective insulin secretory mechanism may not be able to suppress food-intake and will begin to overeat to help stimulate the secretion of insulin. Therefore, he said, the body compensates for low insulin levels by gaining weight. Weight-gain continues, but inadequate insulin levels leave high blood-sugar levels, which can lead to diabetes.

Porte said a recent study suggests that this physiologic defect in insulin secretion is present in some subjects two years before obesity and five years before diabetes. Researchers are now focused on elucidating the specific pathophysiology of the mechanism.

Porte first joined the UW in 1963 as an advanced research fellow under Dr. Robert H. Williams, a renowned endocrinologist and founding chair of the Department of Medicine. From 1971 to 1999, Porte was director of Research and Development for Veterans Affairs Puget Sound Health Care System and from 1977 to 1996, he was director of the UW’s Diabetes Endocrinology Research Center. In January, he joined the VA San Diego Health Care System and the University of California School of Medicine, San Diego.

Will Morton