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
The Departments of Medical Physiology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.
The Departments of Anatomical Pathology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.
J Mol Histol. 2024 Dec 20;56(1):50. 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.
传统的抗糖尿病治疗方法常常存在胰岛β细胞耗竭的风险，这凸显了促进胰岛β细胞再生疗法的必要性。本研究调查了利拉鲁肽、纳曲酮/安非他酮（NTX + BUP）和热量限制对肥胖型2型糖尿病大鼠模型代谢控制和胰岛β细胞再生的比较效果。将50只雄性白化大鼠随机分为五组：正常对照组、糖尿病对照组、糖尿病 + 热量限制组（50%）、糖尿病 + NTX + BUP组（4毫克/45毫克/千克/天，口服）和糖尿病 + 利拉鲁肽组（0.3毫克/千克/天，皮下注射）。评估了体重、体重指数、血糖、胰岛素、血脂谱、致动脉粥样硬化指数、β-抑制蛋白-1水平、胰腺组织病理学以及胰岛素和Ki67的免疫组化染色。与糖尿病对照组相比，所有干预措施均显著改善了体重、体重指数、血糖控制、血脂谱（高密度脂蛋白除外）和致动脉粥样硬化指数。与利拉鲁肽相比，NTX + BUP和热量限制导致体重减轻更多。值得注意的是，与NTX + BUP和热量限制相比，利拉鲁肽显著降低了β-抑制蛋白-1水平。此外，利拉鲁肽和热量限制显著增加了抗胰岛素抗体和Ki67，表明胰岛β细胞再生，而NTX + BUP则显示出不显著的效果。因此我们可以得出结论，虽然NTX + BUP在改善肥胖型2型糖尿病大鼠代谢参数方面显示出疗效，但与利拉鲁肽和热量限制相比，它在促进胰岛β细胞再生方面存在局限性。
