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Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.

  • Thorens B Institute of Pharmacology and Toxicology, 27, rue du Bugnon, CH-1005 Lausanne and Swiss Institute for Experimental Research on Cancer, Ch. des Boveresses, 1066 Epalinges, Switzerland. Bernard.Thorens@ipharm.unil.ch
  • Guillam MT
  • Beermann F
  • Burcelin R
  • Jaquet M
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  • 2000-05-24
Published in:
  • The Journal of biological chemistry. - 2000
Animals
Blood Glucose
Body Weight
Genes, Lethal
Genetic Complementation Test
Glucagon
Glucose
Glucose Clamp Technique
Glucose Tolerance Test
Glucose Transporter Type 1
Glucose Transporter Type 2
Glucose Transporter Type 4
Insulin
Insulin Secretion
Islets of Langerhans
Mice
Mice, Mutant Strains
Mice, Transgenic
Monosaccharide Transport Proteins
Muscle Proteins
RNA, Messenger
Tissue Distribution
English GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse alpha to beta cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic beta cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of alpha to beta cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in beta cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/2220
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