In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes.
Protein expression of an antiaging gene, Klotho, was depleted in pancreatic islets in patients with type 2 diabetes mellitus (T2DM) and in db/db mice, an animal model of T2DM. The objective of this study was to investigate whether in vivo expression of Klotho would preserve pancreatic β-cell function in db/db mice. We report for the first time that β-cell-specific expression of Klotho attenuated the development of diabetes in db/db mice. β-Cell-specific expression of Klotho decreased hyperglycemia and enhanced glucose tolerance. The beneficial effects of Klotho were associated with significant improvements in T2DM-induced decreases in number of β-cells, insulin storage levels in pancreatic islets, and glucose-stimulated insulin secretion from pancreatic islets, which led to increased blood insulin levels in diabetic mice. In addition, β-cell-specific expression of Klotho decreased intracellular superoxide levels, oxidative damage, apoptosis, and DNAJC3 (a marker for endoplasmic reticulum stress) in pancreatic islets. Furthermore, β-cell-specific expression of Klotho increased expression levels of Pdx-1 (insulin transcription factor), PCNA (a marker of cell proliferation), and LC3 (a marker of autophagy) in pancreatic islets in db/db mice. These results reveal that β-cell-specific expression of Klotho improves β-cell function and attenuates the development of T2DM. Therefore, in vivo expression of Klotho may offer a novel strategy for protecting β-cells in T2DM.
Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Yi
Y
Lin
Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK zhongjie-sun@ouhsc.edu.
Zhongjie
Z
Sun
D000818:Animals; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
D007328:Insulin; D013481:Superoxides; D005966:Glucuronidase; D000090265:Klotho Proteins