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Network Models of Type 1 Diabetes

By Lina Sorg

In the human body, the pancreas synchronically secrets insulin and glucagon to control glycaemia, the presence of glucose in the blood. Insulin is a hormone that allows glucose—blood sugar resulting from the breakdown of consumed sugars and starches—to enter the body’s cells and provide the body with energy. When glucose cannot get into the cells, it builds up in the blood stream and can cause long-term complications. In Type 1 diabetes (T1DM), the body produces little to no insulin, because the body’s immune system attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to maintain safe levels of glucose in the blood.

TIDM is usually characterized by lack of insulin, but glucagon amounts are also insufficient; this deficiency results in low blood sugar (hypoglycemia). Leon Farhy, an associate professor in the Division of Endocrinology and Metabolism in the University of Virginia’s Department of Medicine, works in endocrinology to study diabetes. In a presentation titled “Regulation of Glucagon Secretion and Glucagon Counterregulation in Type 1 Diabetes,” part of a minisymposium about diabetes at the SIAM Annual Meeting for the Life Sciences, he proposes an endocrine network model that seeks to replicate the normal glucagon axis by analyzing interactions between blood glucose and the main pancreatic peptides. 

Farhy is particularly interested in investigating the hormonal mechanism that allows cells to combat hypoglycemia in non-diabetic patients, and how the mechanisms differ in patients with TIDM. The model allows him to examine the problems with glucagon management in diabetic patients. Via clinical and experimental in vivo studies, which allow for the mathematical modeling, Farhy’s work shows that the defects in diabetes patients in releasing glucagon and fending off hypoglycemia stem from miscommunication of cells in the pancreas; a lack of cell signaling exists. 

Identifying the problems with glucagon regulation will hopefully help identify strategies for better and safer glycemic control in diabetics. Farhy’s model intends to clarify reasons for glucagon deficiency in TIDM and work towards achieving glucose homeostasis in patients via therapeutic strategies and/or drug treatments.

  Lina Sorg is the associate editor of SIAM News


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