Effectiveness of Course Use of Metformin and its Combination with Intranasal Insulin for Treatment of Rats with “Cafeteria Diet”-Induced Obesity

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Abstract

The “cafeteria diet,” which includes an excess of saturated fats and easily digestible carbohydrates, leads to obesity and is a risk factor for the development of type 2 diabetes. Metformin (MF) is often used to correct diet-induced obesity (DIO), but in some patients it causes serious side effects, which requires a reduction in its doses, including through combined use with drugs that potentiate the effects of MF. A candidate for the role of such drugs is intranasally administered insulin (INI), which itself has a restorative potential in the treatment of metabolic disorders. The goal of the work was to study the effectiveness of a three-week combined use of MF (100 mg/kg/day, perorally) with INI in two doses (1.5 and 6.0 IU/kg/day) for the correction of metabolic and hormonal disorders in male rats with DIO induced by a “cafeteria diet”. It was shown that in rats with DIO, the combination of MF and INI normalized body weight and abdominal fat, restored glucose homeostasis, lipid metabolism, basal and glucose-stimulated levels of insulin and leptin. Compared with MF monotherapy, the combined use of MF and INI more effectively restored sensitivity to insulin, assessed by a decrease in the insulin resistance index, and also normalized glucose tolerance, assessed by a decrease in the value of AUC0-120, 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 the hormonal status of the thyroid system, disturbed in DIO, while the combination of MF with INI at a dose of 6 IU/kg/day worsened the hypothyroid state, mainly due to hyperactivation of thyroid-stimulating hormone secretion and the development resistance of the thyroid gland to it. Thus, for the correction of metabolic and hormonal parameters in DIO, including the restoration of the functions of the thyroid system, the use of MF with relatively low doses of IVI, which does not have a negative effect on the thyroid axis, is promising.

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K. V. Derkach

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Author for correspondence.
Email: derkatch_k@list.ru
Russian Federation, St. Petersburg

I. I. Zorina

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: derkatch_k@list.ru
Russian Federation, St. Petersburg

A. O. Shpakov

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences; St. Petersburg State University

Email: derkatch_k@list.ru
Russian Federation, St. Petersburg; St. Petersburg

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2. Fig. 1. Glucose concentration in the blood of male rats for 120 minutes after glucose loading in an intraperitoneal glucose tolerance test.

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