Pancreas transplantation modulates reverse cholesterol transport

Hyperinsulinemia secondary to insulin-resistance in type-II diabetes or in the metabolic syndrome is associated with the "atherogenetic lipoprotein ph enotype": high triglycerides, small, dense low-density lipoprotein (LDL) ch olesterol, and low high-density lipoprotein (HDL) cholesterol. In contrast, hyperinsulinemia in pancreas-kidney transplant recipients (PKT-R), seconda ry to systemic venous drainage of the heteropically implanted pancreas graf t, leads to high lipoprotein lipase (LPL) activity and a presumably antiath erogenic lipoprotein profile with very attenuated postprandial lipemia, hig h HDL cholesterol, and a preponderance of large-sized HDL (HDL2) and large buoyant LDL particles. We interpret these findings to suggest that in PKT-R , peripheral hyperinsulinemia upregulates LPL activity in peripheral tissue s, which induces rapid clearance of chylomicron triglycerides from plasma a nd, thus, attenuates postprandial lipemia. Low postprandial lipemia allows little net cholesteryl ester transfer from HDL to triglyceride-rich lipopro teins, keeping the levels of the antiatherogenic lipoprotein HDL high and p otentially increasing, thereby reverse cholesterol transport. The type of l ipoprotein metabolism and pattern present in PKT-R is associated with a low cardiovascular risk in the general population; it cannot be excluded, howe ver, that hyperinsulinemia as found in PKT-R may contribute to atherosclero sis by effects unrelated to lipoprotein metabolism.