Intranasal or Intraperitoneal Insulin and Oral Metformin, Given Separately or in Co-administration, Prevent Aggravation of Gastric Erosions in Rat with Type 1 Diabetes

Abstract ID 129289 Poster Board 008 Diabetes remains a pressing issue, and its prevalence is steadily increasing. With the increase in the prevalence of diabetes, the number of severe complications of this disease is also growing. Among them, alongside neuropathy, nephropathy, and retinopathy, is gastropathy. In our previous studies, we demonstrated a significant aggravation of indomethacin (IM)-induced gastric ulceration in rats with type 1 diabetes (T1D). This study aimed to explore pharmacological approaches to reducing and preventing the proulcerogenic effects of T1D. We hypothesized that antidiabetic medications could be effective for this purpose. Currently, standard insulin therapy alone is still not the best treatment for T1D. Metformin, besides use in type 2 diabetes (T2D), might be considered for a treatment of T1D. We compared the effectiveness of insulin, intranasal (i.n.) and intraperitoneal (i.p.), and metformin, given separately or in co-administration, on IM-induced gastric erosions in rats with T1D as well as in control non-diabetic rats. To induce T1D, streptozotocin (STZ, 60 mg/kg, i.p.) was administered once 2 weeks before IM (35 mg/kg, s.c.) in rats. The development of diabetes was assessed by blood glucose levels, changes in the rats' body weight, and water consumption. Insulin (2 IU/kg, i.p. or 0.5 IU/rat, i.n.) and metformin (100 mg/kg, orally) were administered daily, either separately or in co-administration, starting from the 7-8th day after the administration of STZ, for 7 days. After the last administration of the drugs, the rats were fasted for 20 hours before IM administration. Four hours after IM administration, the rats were decapitated, the stomachs were removed to estimate the erosion area; the adrenal glands and thymus were removed to estimate their weight, and trunk blood was collected to test the corticosterone and glucose levels. During the first week after STZ administration characteristic signs of diabetes developed: increased blood glucose, increased water consumption, and slower body weight gain. The development of STZ-induced diabetes was accompanied by the manifestation of signs of chronic stress: an increase in plasma corticosterone level, an increase in the relative weight of the adrenal glands, and a decrease in the relative weight of the thymus. The development of STZ-induced diabetes led to a pronounced worsening of the ulcerogenic effect of IM. Insulin (i.n. and i.p.) and metformin given separately or in co-administration for 7 days prevented the erosion-promoting effect of STZ. In addition, insulin, but not metformin, also had a gastroprotective effect in non-diabetic rats: it reduced the average area of IM-induced erosions. In conclusion, the results obtained indicate that both insulin (i.n. and i.p.) and metformin are highly effective in preventing the proulcerogenic action of T1D, and separate administration of these drugs is sufficient for this purpose. Overall, the findings suggest potential therapeutic benefits of insulin and metformin in managing gastric erosions associated with T1D. Grant for the creation and development of the world-class scientific center "Pavlov Center Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance" and with financial support from the Ministry of Education and Science of the Russian Federation (No 075-15-2022-303, 21.04.2022.)