Efficacy of Metformin Course Application Combined with Intranasal Insulin in Treating Rats with Cafeteria Diet-Induced Obesity

IF 0.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Evolutionary Biochemistry and Physiology Pub Date : 2024-04-26 DOI:10.1134/s0022093024020327

K. V. Derkach, I. I. Zorina, A. O. Shpakov

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Abstract

The so-called cafeteria diet (CD), rich in saturated fats and light fast-digesting carbohydrates, leads to obesity and is a risk factor for type 2 diabetes. Metformin (MF) is often used to correct diet-induced obesity, but in some patients, it elicits serious side effects, which requires dose reduction, including through its co-application with drugs potentiating MF effects. Intranasally administered insulin (INI), which per se has a restorative potential in the treatment of metabolic disorders, is a candidate for the role of such a drug. This work was aimed to study the efficacy of a 3-week combined course of MF (100 mg/kg/day, perorally) and INI (1.5 or 6.0 IU/kg/day) to correct metabolic and hormonal disorders in male rats with CD-induced obesity (CDIO). It was shown that in CDIO rats, the MF + INI combination normalized body weight and abdominal fat, as well as restored glucose homeostasis, lipid metabolism, basal and glucose-stimulated insulin and leptin levels. Compared to MF monotherapy, a combined course of MF + INI application more effectively restored insulin sensitivity, as assessed by a decrease in the insulin resistance index, and normalized glucose tolerance, as assessed by a decrease in AUC_0–120, the integrated area under glucose concentration curves in the glucose tolerance test. The combination of MF with INI at a dose of 1.5 IU/kg/day normalized thyroidal status, disturbed in CDIO, while the combination of MF with INI at a dose of 6 IU/kg/day exacerbated the hypothyroid state, mainly due to hyperactivation of thyroid-stimulating hormone secretion and the development of thyroid resistance to this hormone. Thus, a combined course of MF with relatively low-dose INI, which has no negative effects on the thyroid axis, appears promising for correcting metabolic and hormonal indices in CDIO, including functional restoration of the thyroid system.

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二甲双胍疗程应用联合鼻内胰岛素治疗食堂饮食诱发肥胖大鼠的疗效

摘要所谓的食堂饮食（CD）富含饱和脂肪和清淡的快消化碳水化合物，会导致肥胖，是2型糖尿病的危险因素。二甲双胍（MF）常用于纠正饮食引起的肥胖，但在某些患者中会产生严重的副作用，因此需要减少剂量，包括与增强二甲双胍作用的药物联合应用。鼻内注射胰岛素（INI）在治疗代谢紊乱方面具有恢复潜力，是此类药物的候选者。这项工作旨在研究 MF（100 毫克/千克/天，经口）和 INI（1.5 或 6.0 IU/千克/天）联合治疗 CD 诱导肥胖（CDIO）雄性大鼠代谢和激素紊乱 3 周疗程的疗效。研究表明，在 CDIO 大鼠中，MF + INI 联合疗法可使体重和腹部脂肪恢复正常，并恢复糖稳态、脂代谢、基础和葡萄糖刺激胰岛素和瘦素水平。与 MF 单一疗法相比，MF + INI 联合疗法能更有效地恢复胰岛素敏感性（根据胰岛素抵抗指数的下降评估）和糖耐量正常化（根据糖耐量试验中葡萄糖浓度曲线下积分面积 AUC0-120 的下降评估）。甲状腺纤维素与 INI 的联合用药剂量为 1.5IU/kg/ 天，可使 CDIO 中紊乱的甲状腺状态恢复正常，而甲状腺纤维素与 INI 的联合用药剂量为 6IU/kg/ 天，则会加剧甲状腺功能减退状态，这主要是由于甲状腺刺激激素分泌亢进和甲状腺对该激素产生抗性。因此，甲状腺激素与相对低剂量的 INI（对甲状腺轴无负面影响）联合治疗，似乎有望纠正 CDIO 的代谢和激素指数，包括甲状腺系统的功能恢复。

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来源期刊

Journal of Evolutionary Biochemistry and Physiology 生物-进化生物学

自引率

33.30%

发文量

110

审稿时长

6-12 weeks

期刊介绍： Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.