Immunohistochemical localization of calbindin-D28k in the pancreas of normal and K-ATP channel-deficient mice: Its possible role in the prevention ofcell damage to islet cells

Calbindin-D28k is a predominant calcium-binding protein contained in the pa ncreatic islets. It can buffer Ca2+ rises following stimulation and thereby protect cells against calcium toxicity. Our previous study of ATP-sensitiv e K+ channel (KATP channel)-knockout mice showed that beta cells decreased in both their number and immunoreactivity for insulin, due to the sustained elevation of intracellular Ca2+ concentration, whereas alpha cells also ex pressing KATP channels generally increased in number. The present immunohis tochemical study aims to explain the difference in responses of alpha and b eta cells to the loss of KATP channels. The immunoreactivity for calbindin- D28k was localized in alpha cells in normal mice, but not present in beta c ells. This finding held true in islet cells of the KATP channel-knockout mi ce. An immunohistochemical survey using six rodents including the mouse sho wed that calbindin-D28k was preferentially localized in alpha cells in the rat, guinea pig, and mouse, while in the hamster both alpha and beta cells were rich in calbindin-D28k. None of the alpha and beta cells in the squirr el or gerbil pancreas were immunoreactive for calbindin-D28k. This finding may explain how alpha cells but not beta cells in the knockout mice could e scape from the calcium toxicity, and shows that the cellular localization o f calbindin-D28k in the islets differs even among rodents.