Diabetes is a heterogeneous metabolic disorder associated with high blood glucose levels. Pancreatic β -cells play crucial role in the maintenance of glucose homeostasis by secreting Insulin hormone. Insulin secretion in β-cells is associated with an increase of free intra cellular Ca²⁺ concentration ([Ca²⁺]_i) . Ca²⁺ homeostasis and normal Ca²⁺ signalling are necessary for β-cells to function normally. Multiple mechanisms are involved in the increase of [Ca²⁺]_i in the β-cells, which receive signals from the nutrient metabolism. There are Ca²⁺ pumps, and Ca²⁺ releasing channels on plasma membrane as well as highly structured Ca²⁺ stores that are part of the endoplasmic reticulum in β-cells. These pumps and channels regulate Ca²⁺ signalling that are induced by plasma membrane depolarization, and activation of plasma membrane receptors that are coupled to the phospholipase C system.

Transient receptor potential (TRP) channels are tetrameric ion channels that are classified into seven families. TRP channels are mostly involved in mediating many sensory functions like vision, olfaction, hearing, thermo-sensation, and taste. In β-cells, some of the TRP channels like TRPM2, TRPM5, and TRPV1 are involved in increasing the [Ca²⁺]_i.

Sulphonylureas like tolbutamide have been widely used for treating Type-2 diabetes. The sulphonylureas inhibit the ATP sensitive potassium channels (K_ATP) channels by binding to the sulphonyl urea receptor 1 (SUR1). They decrease the blood glucose levels by secreting insulin. One of the aims of our project was to explore the involvement of TRP channels in tolbutamide-induced Ca²⁺ increase in the S5 cells.

Purinergic receptor 2 (P2Y) receptors are metabotropic, G-proteon coupled receptors. Eight subtypes of P2Y receptors have been discovered.   Intracellular ADPr is found to increase the [Ca²⁺]^­­_i through activation of the TRPM2 channels. However the mechanism involved in [Ca²⁺]^­­_i increase by   extracellular application of ADPr is not clear. We were interested in finding out the cell surface receptor involved in the interaction with ADPr to increase [Ca²⁺]_i.