Metformin can activate imidazoline I-2 receptors to lower plasma glucose in type 1-like diabetic rats
| Autor: | Hung Tsung Wu, King-Chuen Lin, J. T. Cheng, J. P. Lee, Wency Chen |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty endocrine system diseases medicine.drug_class Endocrinology Diabetes and Metabolism Glucose uptake Clinical Biochemistry Imidazoline receptor Pharmacology Biochemistry Endocrinology Diabetes mellitus Internal medicine medicine Animals Humans Hypoglycemic Agents Rats Wistar Receptor Chemistry digestive oral and skin physiology Biochemistry (medical) beta-Endorphin nutritional and metabolic diseases General Medicine medicine.disease Receptor antagonist Metformin Amiloride Rats Disease Models Animal medicine.anatomical_structure Diabetes Mellitus Type 1 Imidazoline Receptors Adrenal medulla medicine.drug |
| Zdroj: | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 43(1) |
| ISSN: | 1439-4286 |
| Popis: | Metformin is widely used in clinic for handling the diabetic disorders. However, action mechanisms of metformin remain obscure. It has recently been indicated that guanidinium derivatives are ligands to activate type-2 imidazoline receptors (I-2 receptors) that can improve diabetes through increment in skeletal muscle glucose uptake. Also, activation of I-2 receptors can increase the release of s-endorphin in diabetic animals. Because metformin is a guanidinium derivative, we were interested in the effect of metformin on I-2 receptors. In the present study, the marked blood glucose-lowering action of metformin in streptozotocin-induced type-1 like diabetes rats was blocked by specific I-2 receptor antagonist, BU224, in a dose-dependent manner. Also, the increase of s-endorphin release by metformin was blocked by BU224 in same manner. A specific competition between metformin and BU224 was observed in isolated adrenal medulla. Otherwise, amiloride at the dose sufficient to block I-2A receptor abolished the metformin-induced s-endorphin release, but only the blood glucose-lowering action of metformin was markedly reduced. In addition, the blood glucose-lowering action of metformin in bilateral adrenalectomized rats was diminished by amiloride at higher doses. These results suggest that metformin might activate imidazoline I-2 receptors while I-2A receptors link the increase of s-endorphin release and I-2B receptors couple to the other actions for lowering of blood glucose in type-1 like diabetic rats. |
| Databáze: | OpenAIRE |
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