Inhibition of the high-affinity glucose transporter GLUT 1 affects the sensitivity to glucose in a hamster-derived pancreatic beta cell line (HIT)

Diabetologia. 1993 Nov;36(11):1204-7. doi: 10.1007/BF00401067.

Abstract

HIT is a hamster-derived beta-cell line which in contrast to normal beta cells that only express the high Km GLUT-2 glucose transporter, also expresses the low Km glucose transporter GLUT 1. In HIT cells the abnormal glucose transport mechanism is associated with a marked shift to the left of the glucose-induced insulin release dose-response curve. We have used this cell model to investigate whether changes in glucose transport affect the glucose-induced insulin release. HIT cells were first incubated with a concentration of cytochalasin B (0.4 mumol/l) that selectively inhibits the GLUT-1 but not the GLUT-2 transporter. The consequences of blocking glucose phosphorylation and insulin release were studied. Exposure to 0.4 mumol/l cytochalasin B for 1 h caused a selective loss of the low Km transport: the calculated Vmax of GLUT 1 was reduced from 1726 +/- 98 to 184 +/- 14 pmol.mg protein-1 5 min-1 (mean +/- SEM, n = 6, p < 0.005), while no major difference in the high Km (GLUT-2) transport was observed. In cytochalasin B exposed HIT cells the glucose phosphorylating activity (due to hexokinase and glucokinase) was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-O-Methylglucose
  • Animals
  • Biological Transport / drug effects
  • Cell Line
  • Cricetinae
  • Cytochalasin B / pharmacology*
  • Glucose / metabolism*
  • Glucose / pharmacology*
  • Glucose Transporter Type 1
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Methylglucosides / metabolism
  • Monosaccharide Transport Proteins / antagonists & inhibitors*

Substances

  • Glucose Transporter Type 1
  • Insulin
  • Methylglucosides
  • Monosaccharide Transport Proteins
  • 3-O-Methylglucose
  • Cytochalasin B
  • Glucose