In vivo pancreatic β-cell-specific expression of antiaging gene klotho

A novel approach for preserving β-cells in type 2 diabetes

Yi Lin, Zhongjie Sun

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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. b-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.

Original languageEnglish (US)
Pages (from-to)1444-1458
Number of pages15
JournalDiabetes
Volume64
Issue number4
DOIs
StatePublished - Apr 1 2015

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Type 2 Diabetes Mellitus
Gene Expression
Islets of Langerhans
Insulin
Glucose
Endoplasmic Reticulum Stress
Autophagy
Proliferating Cell Nuclear Antigen
Superoxides
Hyperglycemia
Transcription Factors
Animal Models
Cell Count
Cell Proliferation
Apoptosis
Proteins

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

In vivo pancreatic β-cell-specific expression of antiaging gene klotho : A novel approach for preserving β-cells in type 2 diabetes. / Lin, Yi; Sun, Zhongjie.

In: Diabetes, Vol. 64, No. 4, 01.04.2015, p. 1444-1458.

Research output: Contribution to journalArticle

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