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- Title
Novel Mechanism for Plasma Glucose-Lowering Action of Metformin in Streptozotocin-Induced Diabetic Rats.
- Authors
Cheng, Juei-Tang; Huang, Ching-Chiu; Liu, I-Min; Tzeng, Thing-Fong; Chang, Chill Jen
- Abstract
To better understand the insulin-independent plasma glucose-lowering action of metformin, we used streptozotocin (STZ)-induced diabetic rats to investigate the possible mechanisms. Oral intake of metformin decreased the plasma glucose of STZ-induced diabetic rats with a parallel increase of plasma β-endorphin-like immunoreactivity (BER). Mediation of opioid μ-receptors in the action of metformin was identified by the blockade of receptors with antagonist in STZ-induced diabetic rats and the failure of action in opioid μ-receptor knockout diabetic mice. Release of BER from adrenal glands by metformin was characterized, using bilateral adrenalectomy and the release of BER from isolated adrenal medulla of STZ-induced diabetic rats. Repeated treatment with metformin in STZ-induced diabetic rats increased the mRNA and protein levels of GLUT-4 in soleus muscle that was blocked by naloxonazine. Reduction of the mRNA or protein levels of hepatic PEPCK was also impeded in the same group of STZ-induced diabetic rats. In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of β-endorphin secretion from adrenal glands to stimulate opioid μ-receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZ-induced diabetic rats.
- Subjects
DIABETES; BLOOD plasma; GLUCOSE; STREPTOZOTOCIN; ANTINEOPLASTIC antibiotics; MEDICAL research
- Publication
Diabetes, 2006, Vol 55, Issue 3, p819
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.55.03.06.db05-0934