Smart Insulin

A team of researchers from Case Western University published an article revealing their invention of a “smart” insulin molecule that binds considerably less to cancer receptors and self-assembles under the skin. To provide a slow-release form of insulin, the compound self-assembles under the skin by “stapling” itself together with zinc ions. Zinc staples connect the pieces of the insulin puzzle together to create a functional protein.

The new insulin molecule is special in that it exhibits reduced binding to a receptor that can drive cell growth, called the IGF (insulin-like growth factor) receptor. Increased levels of circulating IGF-1 have been detected in patients with breast and prostate cancers.

“The goal of all drug therapies is to make therapeutic molecules more selective, in other words, more effective with less complications. We’ve sought to accomplish this with our engineering a new and “smarter” insulin molecule, as the hormone’s primary job is to bind to the key receptors that regulate blood glucose concentration (designated the insulin receptor), not cancer-related receptors,” says Dr. Weiss in a press release from Case Western University School of Medicine.

Research has suggested that increased insulin (either naturally produced or injected) and obesity may be associated with an increased risk of some common cancers, including pancreatic and colon cancer, as well as aggressive prostate cancer in men and breast cancer in women. Evidence suggests that the link between obesity and cancer may involve similar mechanisms that link obesity and diabetes – insulin resistance.

Obesity is known to induce insulin resistance, in which the organs of the body are less able to utilize insulin to move blood glucose into the body’s cells for energy. The body compensates by increasing the amount of insulin produced by the pancreas and therefore increasing circulating levels. Insulin is an important growth factor for body tissues, and may induce cell growth and proliferation in a number of ways.  Cancer is the development of abnormal cells that proliferate (or divide) and grow uncontrollably. Therefore cancer may be related to the high levels of insulin produced by the body in response to obesity. 

The research paper, “Supramolecular Protein Engineering – Design of Zinc-Stapled Insulin Hexamers as a Long Acting Depot,” written by Michael Wiess, MD, PhD, and his colleagues, was highlighted as a “Paper of the Week” by the editors of the Journal of Biological Chemistry.

“It’s quite a novel mechanism. Our team has applied the perspective of biomedical engineering to the biochemistry of a therapeutic protein. We regard the injected insulin solution as forming a new biomaterial that can be engineered to optimize its nano-scale properties,” says Dr.Wiess. He adds, “The notion of engineered zinc staples may find application to improve diverse injectable protein drugs to address a variety of conditions from cancer to immune deficiency.”

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation’s top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School’s innovative and pioneering Western Reserve2 curriculum interweaves four themes–research and scholarship, clinical mastery, leadership, and civic professionalism–to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Eleven Nobel Laureates have been affiliated with the school.

Annually, the School of Medicine trains more than 800 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News &World Report “Guide to Graduate Education.”

The School of Medicine’s primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002.

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Case Western press release

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