Inhibition of pancreatic beta-cell glucokinase by antisense RNA expression in transgenic mice: mouse strain-dependent alteration of glucose tolerance.
We have generated transgenic mice, in either C57BL/6 or C3H background, expressing antisense glucokinase mRNA in beta-cells. The glucose phosphorylating activity at 60 mM glucose in transgenic islets was significantly lower than that in controls, and the insulin secretory response to glucose was lower in transgenic islets than in those of controls in both strains. Following i.p. glucose challenge, higher blood glucose levels were observed in transgenic mice than in controls in the C57BL/6 but not the C3H background. These data suggest that a beta-cell secretory defect, in combination with other undefined genetic factors, causes impaired glucose homeostasis in mice.
Ishihara
H
H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Tashiro
F
F
Ikuta
K
K
Asano
T
T
Katagiri
H
H
Inukai
K
K
Kikuchi
M
M
Yazaki
Y
Y
Oka
Y
Y
Miyazaki
J
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005786:Gene Expression Regulation; D005941:Glucokinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D016372:RNA, Antisense / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D005941:Glucokinase; D005947:Glucose