Engineered enteroendocrine cells secrete insulin in response to glucose and reverse hyperglycemia in diabetic mice

Jaeseok Han, Hyune Hwan Lee, Hyokjoon Kwon, Seungjin Shin, Ji Won Yoon, Hee Sook Jun

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Type 1 diabetes is a metabolic disorder caused by loss of insulin-producing pancreatic β-cells. Expression of insulin in non-β-cells to create β-cell surrogates has been tried to treat type 1 diabetes. Enteroendocrine K cells have characteristics similar to pancreatic β-cells, such as a glucose-sensing system and insulin-processing proteases. In this study, we genetically engineered an enteroendocrine cell line (STC-1) to express insulin under the control of the glucose-dependent insulinotropic polypeptide promoter. We screened clones and chose one, Gi-INS-7, based on its high production of insulin. Gi-INS-7 cells expressed glucose transporter 2 (GLUT2) and glucokinase (GK) and secreted insulin in response to elevated glucose levels in vitro. To determine whether Gi-INS-7 cells can control blood glucose levels in diabetic mice, we transplanted these cells under the kidney capsule of streptozotocin (STZ)-induced diabetic mice and found that blood glucose levels became normal within 2 weeks of transplantation. In addition, glucose tolerance tests in mice that became normoglycemic after transplantation with Gi-INS-7 cells showed that exogenous glucose was cleared appropriately. These results suggest that engineered K cells may be promising surrogate β-cells for possible therapeutic use for the treatment of type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)1195-1202
Number of pages8
JournalMolecular Therapy
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1 2007

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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