Differential effects of liraglutide naltrexone/bupropion, and caloric restriction on metabolic parameters and beta-cell regeneration in type 2 diabetic rat model: role of beta arrestin 1

• Published in: Journal of molecular histology 2024-12, Vol.56 (1), p.50
• Main Authors: Merzeban, Dina H., El Amin Ali, Amani M., Hammad, Reem O., Elmahdi, Mohamed H., Sofi, Marwa A., Mahmoud, Rania H., Metwally, Sayed M., El Ebiary, Ahmed M.
• Format: Article
• Language: English
• Subjects: Animals; Arrestin; Beta cells; beta-Arrestin 1 - metabolism; Biomedical and Life Sciences; Biomedicine; Blood Glucose - metabolism; Body Weight - drug effects; Body weight loss; Bupropion; Bupropion - administration & dosage; Bupropion - pharmacology; Caloric Restriction - methods; Cell Biology; Developmental Biology; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Dietary restrictions; Disease Models, Animal; High density lipoprotein; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - blood; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Life Sciences; Liraglutide - pharmacology; Liraglutide - therapeutic use; Male; Metabolism; Naltrexone; Naltrexone - pharmacology; Original Paper; Rats; Regeneration - drug effects
• ISSN: 1567-2379; 1567-2387; 1567-2387
• DOI: 10.1007/s10735-024-10326-x

Traditional antidiabetic treatments often carry the risk of beta-cell exhaustion, highlighting the need for therapies that promote beta-cell regeneration. This study investigates the comparative effects of Liraglutide, naltrexone/bupropion (NTX + BUP), and caloric restriction on metabolic control and beta-cell regeneration in a rat model of obese type 2 diabetes. Fifty male albino rats were randomized into five groups: normal control, diabetic control, diabetic + caloric restriction (50%), diabetic + NTX + BUP (4 mg/45 mg /kg/day orally), and diabetic + liraglutide (0.3 mg/kg/day, S.C). Body weight, BMI, serum glucose, insulin, lipid profile, atherogenic indices, beta-arrestin-1 levels, pancreatic histopathology, and immunohistochemical staining for insulin and Ki67 were assessed. All interventions significantly improved body weight, BMI, glycemic control, lipid profiles (except HDL), and atherogenic indices compared to the diabetic control group. NTX + BUP and caloric restriction resulted in greater weight loss compared to liraglutide. Of note, liraglutide significantly decreased β-arrestin-1 levels compared to both NTX + BUP and caloric restriction. Furthermore, liraglutide and caloric restriction significantly increased anti-insulin antibodies and Ki67 indicating beta-cell regeneration, while NTX + BUP showed insignificant effects. Thus we can conclude that, while NTX + BUP demonstrates efficacy in improving metabolic parameters in obese type 2 diabetic rats, it shows limitations in promoting beta-cell regeneration compared to liraglutide and caloric restriction.