Does reduced degradation of insulin by the liver cause type 2 diabetes?

LOS ANGELES – In some individuals, reduced degradation of insulin by the liver is the cause of type 2 diabetes mellitus.

^{Doug Brunk/MDedge News}

Dr. Richard N. Bergman

That’s a hypothesis that Richard N. Bergman, PhD, and his colleagues are testing in his lab at the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai Medical Center, Los Angeles.

“More than 50% of insulin secreted into the portal vein is degraded by the liver and never enters the systemic circulation,” Dr. Bergman said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “We have found that if you make an animal insulin resistant with a high fat diet, they degrade less of the insulin. Why is that? They deliver a higher fraction of the insulin into the systemic circulation. One of the answers is that the liver is a gateway for insulin delivery to the systemic circulation.” In fact, when he and his colleagues tested a population of normal dogs, they found wide variability in the ability of the liver to take up and degrade insulin (Diabetes. 2018 67[8]:1495-503).

“It ranged from 20% to 70%; I didn’t believe these data,” said Dr. Bergman, who is also chair in diabetes research at Cedars-Sinai. “We had to redo the study and the same thing was true. There’s a wide variation in what fraction of insulin that enters the liver is degraded. That led to the idea that this could be true in humans.”