Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice.
Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia in diabetic db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA suppresses the elevated hepatic gluconeogenic glucose-6-phosphatase (G6Pase) activity and gene expression in C57BL/KsJ-db/db mice. In the present study, we evaluated the total amount of gluconeogenesis using NaH[(14)C]CO(3) and hepatic glucose production using fructose as a substrate in primary cultured hepatocytes. Despite hyperinsulinemia, the glucose production of db/db mice in the total body and hepatocytes was elevated as compared to their heterozygote littermate C57BL/KsJ-db/+m mice. Administration of DHEA significantly decreased the blood glucose level and increased the plasma insulin level in db/db mice. Administration of DHEA decreased the elevated total body and hepatic glucose production in db/db mice. In addition, the glucose production in the primary cultured hepatocytes of db/db mice was decreased significantly by the direct addition of DHEA or DHEA-S to the medium. These results suggest that administration of DHEA suppresses the elevated total body and hepatic glucose production in db/db mice, and this effect on the liver is considered to result from increased plasma insulin and DHEA or DHEA-S itself.
Aoki
Kazutaka
K
Internal Medicine, Yokosuka Kyousai Hospital, 1-16 Yonegahama-Dori, Yokosuka 238-8558, Japan. aokikazu@ykh.gr.jp
Taniguchi
Hideki
H
Ito
Yuzuru
Y
Satoh
Shinobu
S
Nakamura
Satoru
S
Muramatsu
Kenichi
K
Yamashita
Ryo
R
Ito
Satoshi
S
Mori
Yasumichi
Y
Sekihara
Hisahiko
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006579:Heterozygote; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects
D000276:Adjuvants, Immunologic; D001786:Blood Glucose; D007328:Insulin; D003687:Dehydroepiandrosterone; D005947:Glucose