In health insulin is secreted in discrete insulin secretory bursts from pancreatic beta cells, collectively referred to as beta-cell mass. We sought to establish the relationship between beta-cell mass, insulin secretory-burst mass and hepatic insulin clearance over a range of age-related insulin sensitivity in adult rats. To address this we used a novel rat model with chronically implanted portal vein catheters for which we established the parameters to permit deconvolution of portal vein insulin concentrations profiles to measure insulin secretion and resolve its pulsatile components. We then examined total and pulsatile insulin secretion, insulin sensitivity, hepatic insulin clearance and beta-cell mass in 35 rats aged 2-12 months. With aging, insulin sensitivity declined but euglycemia was sustained by an adaptive increase in glucose-stimulated insulin secretion through the mechanism of a selective augmentation of insulin pulse mass. The latter was attributable to a closely related increase in beta-cell mass (r=0.8, p<0.001). Hepatic insulin clearance increased with increasing portal vein insulin pulse amplitude, damping the delivery of insulin in to the systemic circulation. In consequence the curvilinear relationship previously reported between insulin secretion and insulin sensitivity was extended to both insulin pulse mass and beta-cell mass versus insulin sensitivity. These data support a central role of adaptive changes in beta-cell mass to permit appropriate glucose-stimulated insulin secretion in the setting of decreasing insulin sensitivity in the aging animal. They emphasize the cooperative role of pancreatic beta cells and the liver in regulating the secretion and delivery of insulin to the systemic circulation.