Antidiabetic effects of pterosin A, a small-molecular-weight natural product, on diabetic mouse models.
The therapeutic effect of pterosin A, a small-molecular-weight natural product, on diabetes was investigated. Pterosin A, administered orally for 4 weeks, effectively improved hyperglycemia and glucose intolerance in streptozotocin, high-fat diet-fed, and db/db diabetic mice. There were no adverse effects in normal or diabetic mice treated with pterosin A for 4 weeks. Pterosin A significantly reversed the increased serum insulin and insulin resistance (IR) in dexamethasone-IR mice and in db/db mice. Pterosin A significantly reversed the reduced muscle GLUT-4 translocation and the increased liver phosphoenolpyruvate carboxyl kinase (PEPCK) expression in diabetic mice. Pterosin A also significantly reversed the decreased phosphorylations of AMP-activated protein kinase (AMPK) and Akt in muscles of diabetic mice. The decreased AMPK phosphorylation and increased p38 phosphorylation in livers of db/db mice were effectively reversed by pterosin A. Pterosin A enhanced glucose uptake and AMPK phosphorylation in cultured human muscle cells. In cultured liver cells, pterosin A inhibited inducer-enhanced PEPCK expression, triggered the phosphorylations of AMPK, acetyl CoA carboxylase, and glycogen synthase kinase-3, decreased glycogen synthase phosphorylation, and increased the intracellular glycogen level. These findings indicate that pterosin A may be a potential therapeutic option for diabetes.
Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
Feng-Lin
FL
Hsu
Chun-Fa
CF
Huang
Ya-Wen
YW
Chen
Yuan-Peng
YP
Yen
Cheng-Tien
CT
Wu
Biing-Jiun
BJ
Uang
Rong-Sen
RS
Yang
Shing-Hwa
SH
Liu
D000818:Animals; D001688:Biological Products / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000009:adverse effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000188:drug therapy; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007189:Indans / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects; D012717:Sesquiterpenes / Q000627:therapeutic use*
D001688:Biological Products; D051275:Glucose Transporter Type 4; D007189:Indans; D007328:Insulin; D012717:Sesquiterpenes; C495693:Slc2a4 protein, mouse; C010772:pterosin; D003907:Dexamethasone; D005947:Glucose