Increased levels of free fatty acids in fasted mice stimulate in vivo beta-cell electrical activity

The electrical activity of pancreatic beta-cells in 48-h fasted mice has been recorded in vivo. Their electrical activity is exceedingly high at low levels of blood glucose when compared with control animals. For example, at a blood glucose concentration of 4.5 mmol/l, at which beta-cells are permanently hyperpolarized in control animals, fasted animals show continuous spiking activity. In fasted animals, hyperpolarization only occurs at glycemias below 2.2 mmol/l. As in fed animals, the electrical activity in fasted mice can be decreased or suppressed by the injection of diazoxide, indicating the participation of K(ATP) channels. The treatment of fasted animals with nicotinic acid, an inhibitor of lipolysis, produces a decrease in the levels of free fatty acids (FFAs) and a decrease in electrical activity, thereby restoring the dose-response curve for glucose in fasted animals to values close to those found in fed animals. Conversely, the injection of palmitic acid produces an increase in electrical activity without a change in blood glucose. These results point to FFAs as important regulators of electrical activity during fasting in vivo. They also indicate a dissociation of electrical activity and insulin release in fasted animals, since an increase in electrical activity is not associated with increased insulin secretion.