[Etiology and molecular biology of hyperproinsulinemia]

Clinical hyperproinsulinemia occurs not only in familial hyperproinsulinemia, but also in insulinoma, renal failure, and even in non-insulin-dependent diabetes mellitus (NIDDM). The etiology of hyperproinsulinemia is divided into (1) abnormality of pro-insulin molecules, (2) abnormality of pancreatic beta-cells other than proinsulin molecules, (3) retardation of proinsulin clearance. Hyperproinsulinemia is now thought to be both a result of the above-mentioned diseases and a cause of atherosclerosis in patients with NIDDM. Recent developments in molecular biology have deepened our knowledge of the biosynthesis and role of proinsulin, especially the prohormone sorting mechanism into secretory granules in pancreatic beta-cells.