Islet amyloid polypeptide (amylin) modulates chylomicron metabolism in rats

1. Amylin is a pancreatic peptide that has been shown to be able to induce a state of peripheral insulin resistance. Hyperamylinaemia, which occurs in type 2 diabetes, may be central to a number of metabolic abnormalities present in the diabetic state. Because lipoprotein metabolism is often disturbed in diabetes, we investigated whether amylin was a regulating factor of lipoprotein metabolism in rats; specifically, whether exogenous amylin influences production and clearance of triglyceride (TG)-rich lipoproteins. 2. When amylin was given acutely to rats or by way of infusion, total plasma TG was significantly elevated. Acute doses of amylin decreased fractional clearance rates of TG-rich lipoproteins by 45%. Hydrolysis of lipoproteins by endothelial lipases was not decreased; rather, amylin appeared to reduce hepatic uptake of TG-rich lipoproteins, following conversion to the remnant form. Consistent with the kinetic data in vivo, cell culture studies found that amylin reduced the high-affinity uptake of remnant lipoproteins, probably by inhibiting low-density lipoprotein receptor expression. 3. We have found that amylin can influence the kinetics of TG-rich lipoproteins in vivo and in vitro. Amylin can reduce chylomicron uptake, most probably by regulating lipoprotein receptors either directly, or via modulation of insulin activity. Increased levels of amylin in type 2 diabetes may contribute to the raised concentration of TG-rich remnant lipoproteins present in this disease.