Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.
Glucose homeostasis is controlled by a glucose sensor in pancreatic beta-cells. Studies on rodent beta-cells have suggested a role for GLUT2 and glucokinase in this control function and in mechanisms leading to diabetes. Little direct evidence exists so far to implicate these two proteins in glucose recognition by human beta-cells. The present in vitro study investigates the role of glucose transport and phosphorylation in beta-cell preparations from nondiabetic human pancreata. Human beta-cells differ from rodent beta-cells in glucose transporter gene expression (predominantly GLUT1 instead of GLUT2), explaining their low Km (3 mmol/liter) and low VMAX (3 mmol/min per liter) for 3-O-methyl glucose transport. The 100-fold lower GLUT2 abundance in human versus rat beta-cells is associated with a 10-fold slower uptake of alloxan, explaining their resistance to this rodent diabetogenic agent. Human and rat beta-cells exhibit comparable glucokinase expression with similar flux-generating influence on total glucose utilization. These data underline the importance of glucokinase but not of GLUT2 in the glucose sensor of human beta-cells.
De Vos
A
A
Diabetes Research Center, Faculty of Medicine, Vrije Universiteit Brussel, Belgium.
Heimberg
H
H
Quartier
E
E
Huypens
P
P
Bouwens
L
L
Pipeleers
D
D
Schuit
F
F
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D005941:Glucokinase / Q000096:biosynthesis* / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D051381:Rats
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; C495679:Slc2a1 protein, rat; D005941:Glucokinase; D005947:Glucose