Appetite-Suppressing Effects of Novel Glucoregulatory Chimeric Peptides Devoid of Nausea
Abstract
This project specifically addresses two major Fiscal Year 2019 Peer Reviewed Medical Research Program Areas of Encouragement, i.e., Diabetes and Eating Disorders/Obesity. According to the U.S. Department of Veterans Affairs (VA), one in four Veterans receiving care at VA medical centers has been diagnosed with, primarily, type 2 diabetes mellitus (T2D), with an estimated 61%-83% of Department of Defense (DoD) recipients and ~78% of Veterans receiving VA care also listed as overweight or obese. In 2012, the total costs of diagnosed diabetes mellitus in the U.S. were $245 billion, which included $176 billion for direct medical costs and $69 billion for reduced productivity. However, according to the 2017 VA/DoD clinical guidelines for the management of T2D, direct costs for the military population enrolled in the Military Health System are not known. Although the occurrences of both type 1 diabetes and T2D are increasing around the world, it is T2D that is clearly linked to obesity, unhealthy nutrition, and sedentary lifestyles. Moreover, T2D often goes undiagnosed in the Veteran population, contributing to the development of other associated diseases, including stroke, kidney, and heart disease. People with abdominal obesity have a high risk for insulin resistance and dysfunction of insulin-producing cells in the pancreas, which are major contributors to the development of T2D. The proposed research will contribute to our understanding of the causes and medical consequences of obesity, which include diabetes, and to new treatments of both. In the proposed study, we will test if obesity and its associated complications, such as diabetes, may be prevented or ameliorated by treatment with a single drug. We will evaluate single drug interventions that offer profound weight loss, control blood sugar, and reduce the inflammatory damage to insulin-producing cells, by simultaneously acting at multiple beneficial pathways. Our group has already identified two such drugs, which can act on the glucagon-like peptide-1 receptor (necessary for glucose-dependent insulin release to control blood sugar) and neuropeptide-Y2 receptor (necessary to switch off appetite), which show very promising results with strong reduction of food intake and body weight, improved glucose metabolism, and protection of pancreatic insulin releasing cells from stress due to T2D- or obesity-mediated inflammation. Unlike many treatments available to treat T2D, which cause nausea or vomiting, we noted no such side effects in animal models tested to date, even at concentrations far over those needed to achieve clinically positive outcomes as described above. The goal of the proposed study is to understand the mechanisms behind our potent drug performance and drug safety, to identify mechanisms leading to reduced body weight and improved glucoregulation, and to ensure we have completed the necessary studies to allow us to move into clinical research in humans. The knowledge gained from this research is an important step towards the development of future interventions that reduce food intake, normalize blood glucose levels, increase energy expenditure, and reduce disease progression, all free of unwanted side effects and poor patient compliance. It will aid in the development of clinical strategies for the prevention and cure of obesity and diabetes among VA patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010299
Entities
People
- Christian Roth
Organizations
- United States Army