Metformin and Bee Venom: a Comparative Detection of Histological Alteration of the Pancreas and Systemic Inflammatory Markers in Diabetic Mice.

Metformin is the approved medication for managing global health issues concerning type 2 diabetes mellitus (T2DM). Using natural bioactive compounds as an alternative therapy is crucial to managing several metabolic diseases. Therefore, due to recent limited studies that detected the role of bee venom (BV) in improving diabetic conditions in Iraq, the current study was designed to identify the potential therapeutic role of BV and metformin in diabetic mice. Twenty male mice (Balb/c) aged about 60 days with an average weight of 26.55±2.70 g were randomly divided into four groups (n=5). The animals were placed in plastic cages for acclimatization for one week of access to food and water ad libitum. Overnight fasting was applied to 15 mice which were then injected with 95 mg/kg body weight of prepared alloxan. The mice were supplemented with glucose fluid for 3 days. On day 4, the blood was collected from the tail to measure the circulating glucose level. When blood glucose levels exceed 200 mg/dl, the animals are considered diabetic. After induction of diabetes, the animals were divided as follows: Control group: included five mice that were not subjected to diabetes induction; the animals in this group: did not receive any medications. Diabetic group: including five mice confirmed with diabetes without receiving any treatments. Metformin group: including five diabetic mice exposed to a single oral dose of 150 mg/kg of metformin for 30 days. Bee Venom group: including five diabetic mice exposed to a single intraperitoneal dose of 1 mg/kg Bee Venom for 30 days. After 30 days of treatment, blood was drained, and serum was obtained to detect the levels of glucose, insulin, TNFα, IL6, and IL10 by using precise enzyme-linked immunosorbent assay (ELIZA) kits. Also, the pancreas was collected from all mice for histopathological investigation. The result displayed significantly elevated glucose concentration in diabetic mice, while metformin and BV significantly reversed these increases. A significant decline in insulin concentration was seen in diabetic mice, whereas metformin and BV significantly enhanced this reduction in insulin concentration. Furthermore, mice treated with alloxan exhibited remarkable increases in TNFα and IL6 compared to control mice, while supplemented metformin and BV significantly reduced these high concentrations. Moreover, the level of IL10 markedly declined in diabetic mice, which was reversed significantly in response to metformin and BV. Histological detection of the pancreas in diabetic mice showed significant changes in the shape and size of islets associated with the arrangement and number of beta cells with a reduction of islets covering connective tissue. Metformin slightly restored these alterations; however, significant and remarkable restoring of histological changing was promoted by BV. Thus, BV could be a potential agent for managing metabolic disorders including diabetes.