Positive and negative effects of ion channels blockers on carbohydrate metabolism and diabetes

Ion channels are protein complexes located in the cell membrane that enable the movement of ions across it. Events that affect carbohydrate metabolism can cause an increase or decrease in blood glucose levels. Diabetes is a chronic and complex metabolic disease characterized by impaired carbohydrate, fat, and protein metabolism. The objective of this thesis study is to examine the impact of ion channel blockers on diabetes. The study analysed the diabetic activity of several ion channel blockers, including naringenin, mexiletine, azimilide, diazoxide, diltiazem, and verapamil. The effects of these blockers on intracellular and extracellular ion concentrations, as well as their impact on sugar consumption and enzyme activity of cells, were examined. Spectrophotometric methods were used to determine the inhibition of alpha-amylase and alpha-glycosidase enzymes. For cell culture studies, the concentration of the compound that did not affect cell proliferation was determined using the Alamar Blue method. Subsequently, the concentrations of sodium, potassium, and calcium ions in the intracellular fluid were measured using the inductively coupled plasma spectroscopy (ICP-OES) method. The study on enzyme activity revealed that naringenin, mexiletine, diltiazem, and diazoxide compounds exhibited inhibitory effects, whereas verapamil and azimilide compounds showed activator effects on the α-glycosidase enzyme. The study on α-amylase enzyme showed that naringenin, azimilide, diazoxide, and diltiazem blockers caused activation of this enzyme, while mexiletine and verapamil exhibited inhibitory effects. The study investigated the effects of ion channel blockers on H9c2 and PANC-1 cell lines at high and low sugar ratios in cell culture. The results showed that mexiletine and naringenin promoted sugar consumption in muscle cells in a high glucose environment, while verapamil and diltiazem decreased sugar consumption. Upon evaluating all the results, it is evident that naringenin inhibits the α- glycosidase enzyme. However, it promotes sugar consumption in muscle cells, which may increase blood sugar levels when consumed during meals as it activates the α-amylase enzyme. This suggests that naringenin could be a suitable alternative for diabetic patients. Therefore, it may be recommended to take it at least two hours after meals. Mexiletine, azimilide, and diazoxide are ion channel blockers that have been found to exhibit antidiabetic properties and may be more suitable for diabetic patients than other types of ion channel blockers. This study suggests that ion channel blockers behave differently in diabetic conditions compared to normal conditions. However, further in vivo experiments are needed to provide more conclusive findings. It is important to note that this study's findings are limited and should be interpreted with caution.