ALPHA1-ADRENERGIC RECEPTOR BLOCKING ACTION OF CARVEDILOL CONTRIBUTES TO TACKLING DEXAMETHASONE-INDUCED INSULIN RESISTANCE AND TO A LESSER EXTENT HEPATIC DAMAGE | ||
| Bulletin of Pharmaceutical Sciences Assiut University | ||
| Volume 48, Issue 1, June 2025, Pages 681-696 PDF (946.96 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/bfsa.2024.322563.2288 | ||
| Authors | ||
| Mohamed Alaa Hafez* 1; Enssaf Ahmad Ahmad2; Mona Fouad Mahmoud3; Islam Ahmed Ibrahim4 | ||
| 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt | ||
| 2Lecturer at Department of Human Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt | ||
| 3Professor at Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt | ||
| 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt | ||
| Abstract | ||
| Insulin resistance is a well-established risk factor for serious health problems, including type 2 diabetes, cardiovascular disease, and stroke. Carvedilol has been documented to improve insulin sensitivity, ameliorate hyperlipidemia, and reduce the risk of diabetes. This study aimed to explore the role of α1-adrenergic receptors (α1ARs) in mediating the insulin-sensitizing effect of carvedilol in dexamethasone-treated rats. Insulin resistance was induced by subcutaneous injection of dexamethasone (10 mg/kg) for 7 days in rats. Five groups were used: control; dexamethasone; carvedilol (10 mg/kg); phenylephrine (1 mg/kg); carvedilol and phenylephrine. Serum glucose, insulin, and lipid profiles, as well as hepatic glycogen content, diacylglycerol level, protein kinase B activity, collagen type I, histopathological changes, and β-arrestin2 immunohistochemistry, were measured. The results demonstrated that blocking of α1- and β-ARs by carvedilol mitigated dexamethasone-induced insulin resistance and hepatic damage. Moreover, pre-injection of phenylephrine attenuated the insulin-sensitizing effect of carvedilol and, to a lesser extent, hepatic damage. In conclusion, the α1-blocking action of carvedilol contributes to its insulin-sensitizing effect as well as to its beneficial effect on the lipid profile. On the other hand, the hepatoprotective effect of carvedilol in dexamethasone-treated rats is less dependent on the α1AR. | ||
| Keywords | ||
| α1-adrenergic receptors; Carvedilol; Dexamethasone; Insulin resistance; Phenylephrine | ||
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