Role of islet amyloid in type 2 diabetes mellitus: consequence or cause?
Type 2 diabetes mellitus (DM2) is characterized metabolically by defects in both insulin secretion and insulin action, resulting in hyperglycemia. Histopathologically, DM2 is characterized by depositions of protein in the pancreatic islets. This 'islet amyloid' is present in >90% of patients with DM2, as well as in monkeys and cats with DM2. The pathogenesis of DM2 is heterogeneous and multifactorial, although insulin resistance seems to be the predominant initiating factor for development of the disease. In the longer term, an insulin secretion defect is also revealed (referred to as 'beta-cell failure'), resulting in clinically manifest diabetes. Recent data, particularly from transgenic mouse studies, indicate that islet amyloidosis is a diabetogenic factor, which is both consequence (of insulin resistance) and cause (of beta-cell failure) of DM2. Available transgenic mouse models with islet amyloid formation in vivo will provide the opportunity to assess the effectiveness of novel anti-amyloidogenic therapies, for which promising results are emerging.
Höppener
Jo W M
JW
Department of Clinical Endocrinology, University Medical Center Utrecht, Location University Hospital, G02.228, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. j.w.m.hoeppener@lab.azu.nl
Nieuwenhuis
Maria G
MG
Vroom
Thea M
TM
Ahrén
Bo
B
Lips
Cees J M
CJ
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
D000682:Amyloid; D058228:Islet Amyloid Polypeptide