CYCLIC-AMP TRIGGERS LARGE [CA2-STIMULATED BETA-CELLS FROM OB OB MICE(](I) OSCILLATIONS IN GLUCOSE)

The modulation of intracellular free calcium concentration ([Ca2+]i) b y cAMP was compared in pancreatic beta-cells of lean (+/+) and obese ( ob/ob) mice. Neither forskolin nor 8-bromo-cAMP significantly affected basal [Ca2+]i in unstimulated lean and obese mouse beta-cells. In obe se, but not in lean mouse beta-cells, adding forskolin or 8-bromo-cAMP during the glucose-induced [Ca2+]i response triggered external Ca2+-d ependent [Ca2+]i oscillations with a duration of 5-11 s and a frequenc y of 2.3-4.8 min-1. The induction of oscillations by cAMP required bot h a stimulatory glucose concentration and membrane depolarization. (S( p))-cAMPS, did induce oscillations in lean mouse beta-cells. However, these oscillations were different from those seen in obese mouse beta- cells and required higher concentrations of (S(p))-cAMPS. The inducibi lity of fast oscillations in obese mouse beta-cells indicates hypersen sitivity of these cells to cAMP, and suggests an abnormal behavior of K+ and/or Ca2+ channels.