173b Dynamic Modeling of Fatty Acid, Glucose, and Insulin Interactions


Anirban Roy and Robert S. Parker The pancreas is a very important organ in the human body. The β-cells present in the pancreas secrete insulin in order to facilitate glucose uptake by the body tissues as a substrate for energy. Malfunctioning of these β-cells is the cause of diabetes. There are two types of diabetes: insulin dependent (Type I) and insulin independent (Type II). In Type I diabetes, the pancreas is incapable of secreting any insulin, whereas in Type II diabetes the body either becomes resistant to insulin or the pancreas does not produce sufficient insulin to control glucose concentration. One of the major long term effects of diabetes is hyperglycemia, where the plasma glucose concentration exceeds 120 mg/dl due to a lack of pancreatic insulin secretion. Prolonged hyperglycemia causes kidney disease, blindness, loss of limb, etc. Of more immediate concern in diabetes is hypoglycemia, where the plasma glucose concentration drops below the normal level (< 70 mg/dl). This starving of the cells for fuel can lead to dizziness, unconsciousness or even death. Present clinical approaches to glucose regulation for diabetic patients do not do a satisfactory job in maintaining the plasma glucose level within the normoglycemic range (70 120 mg/dl). For this reason there is a focus on model-based approaches to insulin delivery. The current mathematical models of diabetic patients are predominantly glucocentric (glucose-based); hence, these do not consider the effects of free fatty acid (FFA) metabolism in the body. However, approximately 90% of the muscle energy is derived from fatty acid metabolism when the body is at rest. Further more, significant interactions exist between fatty acid, glucose, and insulin. For instance, recent in vitro studies have shown that continuous hyperglycemia acts as a lipolytic agent thus enhancing the release of stored free fatty acid from adipose tissue into the plasma [1]. On the other hand, insulin acts as an anti-lipolytic agent by promoting the uptake of FFA from the plasma into the adipose tissue for storage as triglycerides [2]. High plasma FFA concentrations reduce insulin-mediated glucose uptake into the liver and periphery [3]. These interactions highlight the importance of fatty acids as metabolites and the necessity for their inclusion in mathematical models of metabolism.

Cite this paper

@inproceedings{Roy2005173bDM, title={173b Dynamic Modeling of Fatty Acid, Glucose, and Insulin Interactions}, author={Anirban Roy and Robert S. Parker}, year={2005} }