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 pre sent in the diabetic state. Because lipoprotein metabolism is often disturb ed in diabetes, we investigated whether amylin was a regulating factor of l ipoprotein metabolism in rats; specifically, whether exogenous amylin influ ences production and clearance of triglyceride (TG)-rich lipoproteins. 2. When amylin was given acutely to rats or by way of infusion, total plasm a 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 reduc e hepatic uptake of TC-rich lipoproteins, following conversion to the remna nt form. Consistent with the kinetic data in vivo, cell culture studies fou nd that amylin reduced the high-affinity uptake of remnant lipoproteins, pr obably by inhibiting low-density lipoprotein receptor expression. 3. We have found that amylin call influence the kinetics of TG-rich lipopro teins in vivo and in vitro. Amylin can reduce chylomicron uptake, most prob ably by regulating lipoprotein receptors either directly, or via modulation of insulin activity. Increased levels of amylin in type 2 diabetes may con tribute to the raised concentration of TG-rich remnant lipoproteins present in this disease.