"A" is for amylin and amyloid in type 2 diabetes mellitus.
Amyloid deposits within the islet of the pancreas have been known for a century. In 1987, the islet amyloid precursor polypeptide (IAPP) amylin (a 37 amino acid) was discovered. Recently there has been an explosion of amylin's importance in the development of type 2 diabetes mellitus (T2DM). This review is intended to share what is understood about amylin derived amyloid and the role it plays in T2DM. Whether islet amyloid is an epiphenomenona, a tombstone, or a trigger it leaves an indelible footprint in greater that 70% of the patients with T2DM. There is current data supporting the damaging role of intermediate sized toxic amyloid particles to the beta cell resulting in a beta cell defect which contributes to a relative deficiency or loss of insulin secretion. Within the islet there is an intense redox stress which may be associated with the unfolding of amylin's native secondary structure compounding its amyloidogenic properties. In addition to the beta cell defect there may be an absorptive defect as a result of amyloid deposition in the basement membranes which form an envelope around the inta-islet capillary endothelium. We have an opportunity to change our current treatment modalities with newer medications and we should attempt to diagnose T2DM earlier and use these newer treatment strategies in combination to decrease glucotoxicity without elevating endogenous insulin and amylin. In the 21st century our goal should be to prevent remodeling, save the pancreatic islet, conquer islet amyloid, and amyloid diabetes.
Hayden
M R
MR
Department of Cardiovascular Atherosclerosis, Metabolism and Aging, Camdenton Community Health Center. Camdenton, MO 65020, USA. mrh29@usmo.com
Tyagi
S C
SC
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008969:Molecular Sequence Data
D000682:Amyloid; D058228:Islet Amyloid Polypeptide