Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phosphatase and fructose-1,6-bisphosphatase activities in C57BL/Ksj-db/db mice: comparison with troglitazone.
The effect of dehydroepiandrosterone (DHEA) on the hepatic and muscle glucose metabolizing enzymes and on blood glucose were investigated in insulin-resistant diabetic C57BL/KsJ-db/db mice and their heterozygote littermates (db/+m). The results were compared with those after troglitazone administration under the same conditions. Despite hyperinsulinemia, hepatic glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities are higher in db/db than in db/+m mice. Dietary administration of DHEA and that of troglitazone for 15 days to respective groups of five mice each significantly decreased blood glucose in db/db mice and hepatic G6Pase and FBPase activities in both db/db and db/+m mice. Hepatic G6Pase and FBPase activities showed a linear relationship with blood glucose in all groups of mice, suggesting that the activities of G6Pase and FBPase are closely related to blood glucose levels. Because androstenedione, a DHEA metabolite, barely affected either of these enzyme activities or blood glucose in db/db mice, the actions of DHEA, which are similar to those of troglitazone, are presumed to be caused by DHEA itself. DHEA is considered to be a modulating agent for the activities of hepatic gluconeogenic enzymes in db/db mice.
Aoki
K
K
Third Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan. caa90130@pop06.odn.ne.jp
Saito
T
T
Satoh
S
S
Mukasa
K
K
Kaneshiro
M
M
Kawasaki
S
S
Okamura
A
A
Sekihara
H
H
D000735:Androstenedione / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000097:blood / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000235:genetics; D004435:Eating / Q000187:drug effects; D006597:Fructose-Bisphosphatase / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D006597:Fructose-Bisphosphatase; D005952:Glucose-6-Phosphatase; D000077288:Troglitazone