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 pho sphorylating activity at 60 mM glucose in transgenic islets was signif icantly lower than that in controls, and the insulin secretory respons e to glucose was lower in transgenic islets than in those of controls in both strains, Following i,p, glucose challenge, higher blood glucos e levels were observed in transgenic mice than in controls in the C57B L/6 but not the C3H background, These data suggest that a beta-cell se cretory defect, in combination with other undefined genetic factors, c auses impaired glucose homeostasis in mice.