| First Author | Cheng JT | Year | 2006 |
| Journal | Diabetes | Volume | 55 |
| Issue | 3 | Pages | 819-25 |
| PubMed ID | 16505249 | Mgi Jnum | J:106857 |
| Mgi Id | MGI:3619684 | Doi | 10.2337/diabetes.55.03.06.db05-0934 |
| Citation | Cheng JT, et al. (2006) Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats. Diabetes 55(3):819-25 |
| abstractText | 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 beta-endorphin-like immunoreactivity (BER). Mediation of opioid mu-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 mu-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 beta-endorphin secretion from adrenal glands to stimulate opioid mu-receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZ-induced diabetic rats. |
