期刊
DIABETES OBESITY & METABOLISM
卷 17, 期 10, 页码 -出版社
WILEY-BLACKWELL
DOI: 10.1111/dom.12529
关键词
amylin; islet amyloid polypeptide (IAPP); peptide inhibitors; type 2 diabetes
资金
- Canadian Institute of Health Research (CIHR)
- CIHR operating grant [MOP-115056]
Increasing evidence points to the cytotoxicity of islet amyloid polypeptide (IAPP) aggregates as a major contributor to the loss of beta-cell mass in type 2 diabetes. Prevention of IAPP formation represents a potential treatment to increase beta-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 beta-cell area leading to improved glucose tolerance. These findings provide support for a key role of islet amyloid in beta-cell survival and validate the application of anti-amyloid compounds as therapeutic strategies to maintain normal insulin secretion in patients with type 2 diabetes.
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