Regulation of [Ca2+]i oscillations in mouse pancreatic islets by adrenergic agonists.
[Ca2+]i oscillations are an important cellular signal in glucose-induced insulin secretion. Isolated mouse pancreatic islets show a high degree of synchronization in their oscillatory pattern. Our comprehensive analysis revealed that 63% of the islets exhibited glucose-induced oscillations with low frequency (< or = 0.5/min) and 37% with high frequency (>0.5/min). The catecholamines adrenaline and noradrenaline as well as clonidine, all known to inhibit insulin secretion, were studied for their ability to modulate the glucose-induced slow large amplitude [Ca2+]i oscillations. All three adrenergic agonists reduced the frequency of the glucose-induced [Ca2+]i oscillations in islets with glucose-induced high frequency [Ca2+]i oscillations, but not in islets, in which glucose induced low frequency [Ca2+]i oscillations. This effect of catecholamines is likely to be mediated via alpha2-adrenoceptors, as supported by the observation that the agonistic effect could be antagonized by yohimbine, a selective alpha2-adrenoceptor antagonist. Thus, whether an individual islet responds to glucose stimulation with high or low frequency [Ca2+]i oscillations appears to be determined at least in part by the adrenergic tone. Furthermore, we could show that glucagon as well as IBMX and forskolin indeed significantly increased the frequency of the glucose-induced [Ca2+]i oscillations. These results support a cAMP mediated regulation and indicate that glucagon release from pancreatic alpha-cells acts in a paracrine fashion as a modulator of glucose-induced [Ca2+]i oscillations in mouse pancreatic islets.
Baltrusch
Simone
S
Institute of Clinical Biochemistry, Hannover Medical School, 30623 Hannover, Germany.
Lenzen
Sigurd
S
D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D005947:Glucose; D002118:Calcium