Effects of tolbutamide on fructose-2,6-bisphosphate formation and ketogenesis in hepatocytes from diabetic rats.
To assess the extrapancreatic action of sulfonylurea directly in the diabetic, effects of tolbutamide on hepatocyte fructose-2,6-bisphosphate (F-2,6-P2) formation and ketone production were investigated using isolated hepatocytes from streptozotocin (STZ)-induced diabetic rats. The basal level of hepatocyte F-2,6-P2 was significantly higher in diabetic rats within 2 weeks after STZ (40 mg/kg body weight) injection compared with that in the nondiabetic control group. Ultimately, a marked decrease in the F-2,6-P2 level was observed at 4 weeks after STZ administration (10% of the control). Although the addition of tolbutamide further increased the hepatocyte F-2,6-P2 level during the first week after STZ injection, no significant effect was observed after the second week and on from the initial STZ. Treatment of diabetes with insulin restored the stimulatory effect of tolbutamide on the hepatocyte F-2,6-P2 formation. Tolbutamide, independently of insulin treatment, lowered the ketone production of hepatocytes from diabetic rats. The present results indicate that insulin is necessary, in advance, for sulfonylurea to stimulate the liver F-2,6-P2 formation, while tolbutamide inhibition of hepatocyte ketone production is independent of insulin. These results provide further support for the role of sulfonylurea in regulating hepatic energy metabolism in the diabetic.
Mori
K
K
Third Department of Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Kaku
K
K
Inoue
H
H
Aoki
M
M
Matsutani
A
A
Kaneko
T
T
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005635:Fructosediphosphates / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D014044:Tolbutamide / Q000494:pharmacology*
D001786:Blood Glucose; D005635:Fructosediphosphates; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; D013311:Streptozocin; C027652:fructose 2,6-diphosphate; D014044:Tolbutamide; D020155:3-Hydroxybutyric Acid