Affecting more than 400 million people worldwide, diabetes is among the most prevalent diseases, particularly in the United States, where almost 30 million people are afflicted. In healthy individuals, insulin, a hormone produced by the beta cells in the pancreas, sends signals throughout the body to remove glucose from the blood, and to use it to synthesize other biomolecules, such as glycogen and triglycerides. In Type I diabetes, the body’s immune system erroneously destroys the beta cells of the pancreas, meaning that insulin production is essentially nonexistent. Individuals with Type II diabetes, in contrast, still have the capability to produce insulin, but do so insufficiently. Through a combination of inadequate physical activity and obesity, these individuals have acquired “insulin resistance,” in which the insulin receptors of the body are desensitized and thus do not adequately perform their function (1). However, localized doses of insulin can overcome this insulin desensitization. Dr. Zhen Gu and his research team of the Joint UNC/NC State Department of Biomedical Engineering, have worked to develop an efficient, specific mechanism of insulin delivery that mitigates the potential complications arising from both Type I and Type II diabetes.
Though the mechanisms by which diabetes can develop differ, the long term complications are the same. These complications, including severe damage to the cardiovascular system, kidneys, and nerves, account for the elevated risk of hospitalization faced by diabetics. While diabetes is often thought of as a mild disease, failure to manage blood glucose levels could result in dependency on dialysis due to kidney failure or the amputation of a lower extremity, resulting from a necrotic ulcer a diabetic patient simply was not aware of due to nerve damage (2). For Type II diabetics, blood glucose levels are chiefly managed with the implementation of more physical exercise and a healthier diet consisting of fewer animal products and more high-fiber, low-fat foods (3). While diet management and exercise can mitigate high blood glucose, some Type II diabetics do require medications that typically act to either stimulate insulin production, elevate the body’s sensitivity to insulin, or reduce serum glucose levels.
Type I diabetics, on the other hand, are completely insulin dependent, and require self-administration of insulin via pumping or injections into the abdomen or upper thigh. While dietary management and exercise can regulate their serum glucose levels, Type I diabetics are unconditionally bound to insulin administration (4). Furthermore, Type II patients may also require insulin therapy to properly regulate blood sugar to mitigating the risks associated with the disease.
Thanks to a collaborative effort from Dr. Gu and his joint research team at the University of North Carolina-Chapel Hill and North Carolina State University, the administration of insulin via external mechanisms may soon be replaced. Dr. Gu has directed the development of artificial beta cells, or “AβCs.” These “cells,” composed of a simple lipid bilayer, contain a high concentration of insulin-containing vesicles. In response to high blood glucose levels, the membranes of these AβCs undergo a change that permits the passive diffusion of glucose into the bilayer’s interior, which in turn facilitates the release of insulin from the vesicle to the body (5). The principal benefit of such a mechanism of insulin release is its sensitivity to physiologic glucose. Both insulin injections and medications regulating blood glucose are effective only when administered in an appropriate time frame relative to a meal. In other words, if the treatment is applied too far ahead of or too far after a meal, it will not be as effective. AβCs, however, mimic the function of pancreatic beta cells, and thus respond immediately and proportionately to the patient’s blood glucose levels.
In trials conducted on mice genetically modified to lack pancreatic beta cells, a single dose of AβC was shown to lower high blood sugar levels back to a normal physiologic level, and maintain that normal level for a period of five days without the administration of any successive dose. While clinical trials are still far from implementation, Gu plans to develop a method of administering the AβCs via a skin patch that could be replaced after a five day period (6). Applying these recently developed AβCs in such a way could enhance the care afforded to both Type I and Type II diabetics. Instead of constantly monitoring blood glucose levels and continuously administering insulin or glucose regulators prior to meals, patients would be able to apply the patch to themselves and change it once every five days. While dietary regulations and increased physical activity would still need to be implemented to alleviate the risks of hyperglycemia, the administration of artificial beta cells through a dermal patch could minimize the potential for human error to negatively impact diabetic treatment. As Dr. Gu continues his research into the application of AβCs, he has the potential to assuage the burden of diabetes borne by more than 400 million individuals worldwide.
1) Stoppler, Melissa Conrad M.D. “Diabetes Symptoms (Type 1 and Type 2).” https://www.medicinenet.com/diabetes_mellitus/article.htm#diabetes_type_1_and_type_2_definition_and_facts
2) Broersma, A. “Preventing Amputations in patients with diabetes and chronic kidney disease.” Neprhol Nurs J. 2004.
3) Mayo Clinic Staff. “Type 2 Diabetes: Symptoms, Causes, Diagnosis, and Treatment.” https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/diagnosis-treatment/drc-20351199
4) Mayo Clinic Staff. “Type 1 Diabetes: Symptoms, Causes, Diagnosis, and Treatment.” https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/diagnosis-treatment/drc-20353017
5) Derewicz, Mark. “Smart Artificial Beta Cells Could Lead to New Diabetes Treatment.” UNC Healthcare and UNC School of Medicine. 2017. http://news.unchealthcare.org/news/2017/october/smart-artificial-beta-cells-could-lead-to-new-diabetes-treatment
6) Jicheng Yu, Yuqi Zhang, Hunter Bomba and Zhen Gu. “Stimuli-responsive delivery of therapeutics for diabetes treatment.” Bioeng Trans Med. 2016.