PANCREATIC-ISLET AMYLOID FORMATION IN PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS - IMPLICATION FOR THERAPEUTIC STRATEGY

Islet amyloid polypeptide (IAPP or amylin) is the main component of pa ncreatic islet amyloid found in the vast majority of patients with non insulin-dependent (Type-2) diabetes mellitus (NIDDM). IAPP may also ac t as a hormone that antagonizes the effects of insulin on peripheral t issues, but the results with IAPP overproducing transgenic mice and ot her recent findings indicate that IAPP overproduction is unlikely to i nduce peripheral insulin resistance in NIDDM. However, IAPP may contri bute to the progression of NIDDM by impairing beta-cell function via i slet amyloid formation. This may be initiated by locally elevated IAPP concentrations, induced by insulin-resistance-associated beta-cell hy peractivity. In order to improve therapeutic results, we propose strat egies to inhibit IAPP production and islet amyloid formation during th e pathogenesis of NIDDM.