Pancreatic beta-cells from obese-hyperglycemic mice are characterized by excessive firing of cytoplasmic Ca2+ transients.
Pancreatic beta-cells from obese-hyperglycemic (ob/ob) mice are widely used for studying the mechanisms of insulin release, including its regulation by the cytoplasmic Ca2+ concentration ([Ca2+]i). In this study, we compared changes of [Ca2+]i in single beta-cells isolated from ob/ob mice with those from lean mice using dual-wavelength microfluorometry and the indicator fura-2. There were no differences in the frequency, amplitude, and half-width of the slow oscillations induced by glucose. Most beta-cells from the obese mice responded to 10 mM caffeine with transformation of the oscillations into sustained elevation of [Ca2+]i, a process counteracted by ryanodine. The beta-cells from the obese mice were characterized by ample generation of [Ca2+]i transients, which increased in number in the presence of glucagon. The transients became less frequent when leptin was added at a concentration as low as 1 nM. It is suggested that the excessive firing of [Ca2+]i transients in the ob/ob mice is owing to the absence of leptin and is mediated by activation of the phospholipase C signaling pathway.
Ahmed
M
M
Department of Medical Cell Biology, Uppsala University, Sweden.
Grapengiesser
E
E
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020738:Leptin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D020738:Leptin; D012433:Ryanodine; D002110:Caffeine; D005934:Glucagon; D010738:Type C Phospholipases; D002118:Calcium