The aim of the study was to investigate the effect of dietary restriction on the development of insulin resistance, an established precursor to Type 2 Diabetes. This was investigated in conjunction with the effects of both age and diet in a mouse model. The mice were separated into 16 cohorts according to the implementation of dietary restriction or unrestricted access to food (DR or AL, respectively), being fed either a high-fat (HF) or a low fat (LF) diet, as well as the age at which the Oral Glucose Tolerance Test (OGTT) was performed (4, 9, 15, or 21 months of age). The OGTT was performed using a glucose bolus consisting of both unlabelled (natural) glucose as well as deuterium labelled glucose ([6,6-2H2]-glucose). Blood plasma glucose and insulin concentrations were measured for a 2-hour interval following administration of the glucose bolus. A mathematical model consisting of 2 compartments, the Gastrointestinal (GI) and Plasma compartments was used to mathematically model the appearance and disappearance of glucose in the blood plasma. This was achieved using mass action kinetics to describe the transport of glucose from the GI compartment into the blood plasma compartment, as well as its subsequent removal. The contribution of the liver to plasma glucose concentrations was also included as the endogenous glucose production (EGP). Plasma glucose concentrations were then described as functions of time and fit to the OGTT time course data. The parameters obtained from these fitted functions were then used in conjunction with the measured plasma insulin concentrations to calculate Peripheral and Liver specific insulin sensitivity indices (ISP and ISL, respectively). The ISP is calculated using the quotient of the rate of elimination of labelled glucose from the plasma compartment as well as the average insulin concentration throughout the OGTT. In this way, lowered insulin concentrations in conjunction with elevated rates of glucose elimination indicate elevated sensitivity to insulin. The calculated ISP showed DR strongly increased sensitivity, with advanced age and a HF diet only dampening this effect but not preventing it. The ISL is calculated using the average measured plasma insulin concentrations and the average calculated EGP during the time course. Consequently, reduced EGP in conjunction with reduced plasma insulin concentrations indicate an elevated response of the liver to insulin and subsequently a high ISL. The calculated ISL showed DR strongly elevated sensitivity independent of both advanced age and diet. This study highlights the substantial improvement in insulin sensitivity caused by DR, its subsequent reduction in insulin resistance and lowered risk of developing Type 2 Diabetes, as well as the differential effect DR has on both peripheral and hepatic insulin sensitivity.