Glucose Metabolism Regulates Cytosolic Ca²⁺ in the Pancreatic β-Cell by Three Different Mechanisms

Abstract

The main stimulus to promote insulin release is an increase in the extracellular glucose concentration. It has been repeatedly shown that glucose and other secretagogues induced an increase in cytosolic Ca²⁺ ([Ca²⁺]_i). The sequence of events linking exposure to stimulatory glucose concentrations with the release of insulin has been established [1]. Glucose-induced [Ca²⁺]_i increase is a consequence of glucose metabolism, ATP generation and blockade of ATP-dependent K⁺ channels [2,3] which in turn depolarize the cell and activate voltage-dependent Ca²⁺ channels [4]. According to this mechanism it was demonstrated that glucose-induced [Ca²⁺]_i oscillations [5] are due to bursting of the electrical activity [6]. Moreover, simultaneous measurement of K_ATP channel activity and [Ca²⁺]_i in isolated β-cells showed that blockade of K_ATP always precedes [Ca²⁺]_i increase and that there is a strict correlation between spike frequency and Ca²⁺ increase [7]. All this body of theory was in apparent contradiction with other results which indicate that under certain conditions glucose decreased [Ca²⁺]_i [8]. It should be noted that the physiological effect of glucose on [Ca²⁺]_i is neither a decrease nor a steady-state increase in [Ca²⁺]_i but the induction of well-shaped [Ca²⁺]_i oscillations in islet cells. A detailed description of such oscillations is given in Chapter 26.