FLAVONOIDS AS ANTI-DIABETICS

 FLAVONOIDS AS ANTI-DIABETICS

The causes of diabetes can be attributed to various factors. Type 1 diabetes is typically caused by genetic mutations or hereditary factors that result in lower insulin production. On the other hand, Type 2 diabetes can be caused by a combination of factors such as poor eating habits, a sedentary lifestyle, and insulin resistance caused by excessive insulin secretion or chronic inflammation, which may lead to autoimmune disorders. It's important to note that these are general causes, and individual cases may vary. Modifying one's regular eating habits can also contribute to the onset of the disease. Additionally, insulin resistance can occur due to excessive insulin secretion or as a result of chronic inflammation, potentially leading to autoimmune disorders. Flavonoids have been studied for their potential role in managing diabetes and its associated complications. The mechanism of action of flavonoids as anti-diabetic agents involves multiple pathways and mechanisms within the body. At the same time, the exact mechanisms may vary depending on the specific flavonoid compound and the type of diabetes. The following are some common ways in which flavonoids exert their anti-diabetic effects: Insulin Sensitization: Flavonoids can enhance insulin sensitivity, allowing cells to respond more effectively to insulin. They achieve this by activating signaling pathways involved in insulin signaling, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Improved insulin sensitivity promotes glucose uptake by cells and helps regulate blood sugar levels. Pancreatic β-Cell Protection: Flavonoids have been shown to protect pancreatic β-cells, which are responsible for producing and secreting insulin. They help maintain β-cell function, prevent β-cell death, and promote insulin secretion. This effect contributes to the overall regulation of blood glucose levels. Inhibition of Carbohydrate Digestion: Some flavonoids, such as flavonoid glycosides, can inhibit the activity of enzymes involved in carbohydrate digestion, particularly alpha-amylase and alpha-glucosidase. By slowing down the breakdown of complex carbohydrates into simple sugars, flavonoids can reduce the rate of glucose absorption from the digestive tract, leading to better blood glucose control. Antioxidant and Anti-inflammatory Effects: Flavonoids exhibit potent antioxidant and anti-inflammatory properties, which are beneficial in managing diabetes. By reducing oxidative stress and inflammation, flavonoids help protect against cellular damage, improve insulin sensitivity, and mitigate complications associated with diabetes. Modulation of Glucose Transporters: Flavonoids can influence the expression and activity of glucose transporters, such as GLUT4, which are responsible for facilitating glucose uptake into cells. By promoting the translocation of glucose transporters to the cell surface, flavonoids enhance glucose uptake and utilization by tissues. Quercetin reduced glucokinase GLUT4 activity and also decreased hepatic gluconeogenesis and glycogenolysis and enhanced cell survival-related genes and the proliferation of liver in streptozotocin (STZ)-induced diabetic rats. Quercetin with sitagliptin improved β-cell function, glycemic control, metabolic profile, oxidative, and inflammatory activities in STZ-induced diabetic rats. Regulation of Gluconeogenesis: Flavonoids may regulate the production of glucose by the liver through the inhibition of key enzymes involved in gluconeogenesis, the process by which glucose is synthesized from non-carbohydrate sources. This regulation helps maintain optimal blood glucose levels. Rutin is one of the most effective flavonoids against diabetes. It is shown to reduce fasting blood glucose, improve glucose tolerance, and also reduce serum lipids more effectively. It is also observed to activate hepatic enzymes hexokinase, reduce gluconeogenesis, and improve lipid metabolism. Rutin treatment reduces glycosylated hemoglobin and fasting blood glucose levels in STZ-induced diabetic rats. Rutin was also observed to reduce caspase-3 activity by enhancing BCL-2 activity in the diabetic retina.