title: Islet amyloid inhibitors improve glucose homeostasis in a transgenic mouse model of type 2 diabetes.
abstract: Increasing evidence points to the cytotoxicity of islet amyloid polypeptide (IAPP) aggregates as a major contributor to the loss of β-cell mass in type 2 diabetes. Prevention of IAPP formation represents a potential treatment to increase β-cell survival and function. The IAPP inhibitory peptide, D-ANFLVH, has been previously shown to prevent islet amyloid accumulation in cultured human islets. To assess its activity in vivo, D-ANFLVH was administered by intraperitoneal injection into a human IAPP transgenic mouse model, which replicates type 2 diabetes islet amyloid pathology. The peptide was a potent inhibitor of islet amyloid deposition, resulting in reduced islet cell apoptosis and preservation of β-cell area leading to improved glucose tolerance. These findings provide support for a key role of islet amyloid in β-cell survival and validate the application of anti-amyloid compounds as therapeutic strategies to maintain normal insulin secretion in patients with type 2 diabetes.
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Wijesekara
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Ahrens
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Ha
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: M B
authors.initials: MB
authors.lastname: Wheeler
authors.affiliation: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D006706:Homeostasis / Q000187:drug effects*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide
keywords: amylin; islet amyloid polypeptide (IAPP); peptide inhibitors; type 2 diabetes