Rola fosfodiesterazy 3B w regulacji sekrecji insuliny u szczura (Rattus norvegicus Berkenhout)
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2016
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The role of phosphodiesterase 3B in the regulation of insulin secretion in rat (Rattus norvegicus Berkenhout)
Abstract
Fosfodiesteraza 3B wykazuje wysoki poziom ekspresji w komórkach β trzustki i odgrywa istotną rolę w regulacji sekrecji insuliny. W badaniach wykorzystano inhibitor PDE 3B – amrinon, aby stwierdzić czy wzrost stężenia cAMP powodowany inhibicją tego enzymu może nasilać wydzielanie insuliny. Doświadczenia in vitro oraz in situ przeprowadzono na szczurach z grupy kontrolnej oraz z indukowaną eksperymentalnie cukrzycą. W badaniach in vitro, przeprowadzonych na zwierzętach grupy kontrolnej, wykazano wzrost wydzielania insuliny spowodowany amrinonem, jednak jedynie w przypadku fizjologicznego stężenia glukozy (6,7 mM). Zjawisku temu towarzyszył wzrost stężenia cAMP w wyspach trzustkowych, wynikający z zahamowania aktywności PDE 3B. Podwyższoną sekrecję insuliny pod wpływem amrinonu obserwowano również w doświadczeniach in situ. Odmienny rezultat odnotowano w badaniach przeprowadzonych na szczurach z indukowaną eksperymentalnie cukrzycą. Ponadto, pomiar stężenia cAMP w wyspach szczurów cukrzycowych wykazał bardzo wyraźne obniżenie stężenia tego nukleotydu w porównaniu do wysp pochodzących od szczurów z grupy kontrolnej. Uzyskane wyniki wykazały, że PDE 3B pełni istotną rolę w procesie wydzielania insuliny. Niniejsze badania wskazują, że selektywna inhibicja PDE 3B jest jednak niewystarczająca do pobudzenia sekrecji insuliny in vitro oraz in situ w zastosowanym modelu cukrzycy.
The phosphodiesterase 3B is highly expressed in B-cells of pancrease and plays an important role in the regulation of glucose metabolism leading to increased insulin secretion. In this research PDE 3B inhibitor - amrinone has been used to find if increased cAMP levels, resulting from inhibition of PDE 3B, can amplify insulin secretion. The present work was undertaken to determine effects by amrinone on insulin secretion from pancreatic islets and perfused pancreas of normal and mildly diabetic rats. In vitro studies demonstrate that insulin secretion induced by 6.7 mM glucose was significantly increased by inhibitor of PDE 3B from islets of normal rats. This was accompanied by increasing concentration of the cAMP in isolated pancreatic islets resulting from inhibition of activity PDE 3B. Similar effect was observed in pancreatic perfusion in situ. Conversely to islets of control rats, amrinone failed to increase glucose-induced insulin secretion from pancreatic islets of diabetic rats. It was not observed any changes in insulin secretion in vitro and in situ experiments. Moreover amrinone failed to affect cAMP levels in islets of diabetic rats and its content was significantly decreased. The results of the present study demonstrated that amrinone action is insufficient to improve insulin secretion in in vitro and in situ experiments carried out on used model of diabetes.
The phosphodiesterase 3B is highly expressed in B-cells of pancrease and plays an important role in the regulation of glucose metabolism leading to increased insulin secretion. In this research PDE 3B inhibitor - amrinone has been used to find if increased cAMP levels, resulting from inhibition of PDE 3B, can amplify insulin secretion. The present work was undertaken to determine effects by amrinone on insulin secretion from pancreatic islets and perfused pancreas of normal and mildly diabetic rats. In vitro studies demonstrate that insulin secretion induced by 6.7 mM glucose was significantly increased by inhibitor of PDE 3B from islets of normal rats. This was accompanied by increasing concentration of the cAMP in isolated pancreatic islets resulting from inhibition of activity PDE 3B. Similar effect was observed in pancreatic perfusion in situ. Conversely to islets of control rats, amrinone failed to increase glucose-induced insulin secretion from pancreatic islets of diabetic rats. It was not observed any changes in insulin secretion in vitro and in situ experiments. Moreover amrinone failed to affect cAMP levels in islets of diabetic rats and its content was significantly decreased. The results of the present study demonstrated that amrinone action is insufficient to improve insulin secretion in in vitro and in situ experiments carried out on used model of diabetes.
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cukrzyca, diabetes mellitus, sekrecja insuliny, insulin secretion, fosfodiesteraza 3B, phosphodiesterase 3B, wyspy trzustkowe, pancreatic islets