The aim of this study was to examine the effects of
dehydroeburicoic acid (TT) on
type 1 diabetes mellitus and
dyslipidemia in
streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were randomly divided into six groups and given orally by gavage TT (at three dosages),
metformin (Metf), fenfibrate (Feno), or vehicle for 4 weeks. STZ-induced diabetic mice showed elevations in
blood glucose levels (P < 0.001). TT treatment markedly decreased
blood glucose levels by 42.6-46.5%. Moreover, STZ-induced diabetic mice displayed an increase in circulating
triglyceride (TG) and total
cholesterol (TC) levels (P < 0.001 and P < 0.01, respectively) but a decrease in blood
insulin and
adiponectin levels (P < 0.01 and P < 0.05, respectively). These substances are also reversed by TT treatment, indicating TT ameliorated diabetes and
dyslipidemia. Membrane skeletal muscular expression levels of
glucose transporter 4 (GLUT4) and expression levels of AMPK phosphorylation (phospho-AMPK) in both liver and skeletal muscle were reduced in STZ-induced diabetic mice, which normalized upon TT treatment and correction of
hyperglycemia accompanied with a decrease in
mRNA levels of
phosphoenolpyruvate carboxykinase (PEPCK) and
glucose-6-phosphatase (G6 Pase), which was related to the inhibition of hepatic
glucose production and attenuating diabetic state. In addition, TT also showed hypolipidemic effect by increasing hepatic expression levels of
peroxisome proliferator-activated receptor α (PPARα) and
mRNA levels of
carnitine palmitoyl
transferase Ia (CPT-1a) but decreasing expression levels of
fatty acid synthase (FAS), which further contributed to a decrease in circulating TG levels. TT-treated mice displayed decreased SREBP2
mRNA levels and reduced blood TC levels. These findings strongly support that TT prevents diabetic and dyslipidemic states in STZ-induced diabetic mice evidenced by regulation of GLUT4, PPARα, FAS, and phosphorylation of AMPK.