Genetic engineering of glucose-stimulated insulin secretion in Chinese hamster ovary cells

Artif Cells Blood Substit Immobil Biotechnol. 1998 Jul;26(4):329-40. doi: 10.3109/10731199809117675.

Abstract

To engineer an a non-islet cell capable of glucose-stimulated insulin secretion, a chinese hamster ovary cell line (CHO) was transfected with a mammalian expression vector carrying the human insulin cDNA (pCB/hINS). More proinsulin than insulin was released daily by the stably transformed cell line (CHO-INS). Examination of acid-ethanol extracts confirmed that both insulin and proinsulin were stored. Immunohistochemical analysis of the cells also showed that (pro)insulin was stored. Unlike beta cells, CHO-INS cells did not secrete insulin in response to glucose. To investigate this lack of effect, we examined whether transfection of GLUT2 cDNA, which is ordinarily not expressed in CHO-INS cells, would confer glucose-stimulated insulin secretion. Consequently, we have demonstrated that glucose regulated insulin release occurs in the CHO-INS-GLUT2 cell line and that glucose potentiates the insulin secretory response to non-glucose secretagogues.

MeSH terms

  • Animals
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • DNA, Complementary
  • Genetic Engineering
  • Glucokinase / physiology
  • Glucose / pharmacology*
  • Glucose Transporter Type 2
  • Humans
  • Insulin / genetics*
  • Insulin / metabolism*
  • Insulin Secretion
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / physiology
  • RNA, Messenger / analysis
  • Transfection

Substances

  • DNA, Complementary
  • Glucose Transporter Type 2
  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Glucokinase
  • Glucose