Cyclic AMP triggers large [Ca2+]i oscillations in glucose-stimulated beta-cells from ob/ob mice.
The modulation of intracellular free calcium concentration ([Ca2+]i) by 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 obese, but not in lean mouse beta-cells, adding forskolin or 8-bromo-cAMP during the glucose-induced [Ca2+]i response triggered external Ca(2+)-dependent [Ca2+]i oscillations with a duration of 5-11 s and a frequency of 2.3-4.8 min-1. The induction of oscillations by cAMP required both a stimulatory glucose concentration and membrane depolarization. (Sp)-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 (Sp)-cAMPS. The inducibility of fast oscillations in obese mouse beta-cells indicates hypersensitivity of these cells to cAMP, and suggests an abnormal behavior of K+ and/or Ca2+ channels.
Fournier
L
L
Department of Biochemistry, University of Ottawa, Canada.
Whitfield
J F
JF
Schwartz
J L
JL
Bégin-Heick
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese / Q000378:metabolism*; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology
D015221:Potassium Channels; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D002118:Calcium