About: Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice

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About: Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice
Creator	Lazartigues, Eric Chodavarapu, Harshita Porretta, Constance Pedersen, Kim Robinson, Leonie
Source	PMC
abstract	Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse models: db/db mice and angiotensin II-infused mice. A disintegrin and metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane. The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in pancreatic islets and β-cells. Dynamics of ADAM17-mediated ACE2 shedding were investigated in 832/13 insulinoma cells. Within a wide range of ACE2 expression levels, including the level observed in mouse pancreatic islets, overexpression of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels. We provide a mathematical description of shed and cellular ACE2 activities as a function of the ADAM17 activity. The effect of ADAM17 on the cellular ACE2 content was relatively modest with an absolute control strength value less than 0.25 and approaching 0 at low ADAM17 activities. Although we found that ADAM17 and ACE2 are both expressed in pancreatic islets, the β-cell is not the major cell type expressing ACE2 in islets. During diabetes progression in 8-, 12-, and 15-week-old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not decreased over time nor significantly decreased compared with nondiabetic db/m mice. Levels of ADAM17 mRNA and ADAM17 activity were also not significantly changed. Inhibiting basal ADAM17 activity in mouse islets failed to affect ACE2 levels. We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does not deplete ACE2 from pancreatic islets in diabetic db/db mice.
has issue date	2015-12-01(xsd:dateTime)
bibo:doi	10.1210/en.2015-1556
bibo:pmid	26441236
has license	bronze-oa
sha1sum (hex)	37b7e6763e75ccd26ac1153104a4fcac2ae93805
schema:url	https://doi.org/10.1210/en.2015-1556
resource representing a document's title	Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice
has PubMed Central identifier	PMC4655210
has PubMed identifier	26441236
schema:publication	Endocrinology
resource representing a document's body	covid:37b7e6763e75ccd26ac1153104a4fcac2ae93805#body_text
is schema:about of	named entity 'ACE2' named entity 'ADAM17' named entity 'levels' named entity 'ADAM17' named entity 'cell' named entity 'ACE2' named entity 'ADAM17' named entity 'ACE2' named entity 'ACE2' named entity 'ACE2' named entity 'cell membrane' named entity 'Dynamics' named entity 'Pedersen' named entity 'levels' named entity 'ACE2' named entity 'TIME' named entity 'MOUSE ISLETS' named entity 'INHIBITING' named entity 'OBSERVED' named entity 'PROVIDE' named entity 'RANGE' named entity 'IMPROVES' named entity 'PROGRESSION' named entity 'CELL MEMBRANE' named entity 'THE CELL' named entity 'DETERMINE' named entity 'DIABETIC' named entity 'EFFECT' named entity 'WEEK' named entity 'MATHEMATICAL' named entity 'ANGIOTENSIN II' named entity 'ORG' named entity 'STUDIES' named entity 'CHANGED' named entity 'DYNAMICS' named entity '90%' named entity 'MRNA' named entity 'DECREASES' named entity 'STRENGTH VALUE' named entity 'ABSOLUTE' named entity 'OLD' named entity 'ADAM17' named entity 'GLUCOSE REGULATION' named entity 'ACTIVITY LEVELS' named entity 'ACTIVITIES' named entity 'OVEREXPRESSION' named entity 'ACE2' named entity 'CAUSE' named entity 'FUNCTION' named entity 'INCLUDING' named entity 'MODEST' named entity 'INCREASES' named entity 'COMPARED' named entity 'WIDE' named entity 'OUR' named entity 'MICE' named entity 'MEDIATED' named entity 'PANCREATIC ISLETS' named entity 'LEVELS' named entity 'EXPRESSION' named entity 'SHEDDING' named entity 'MEDIATED' named entity 'ENDOCRINOLOGY' named entity 'MOUSE MODELS' named entity 'EXPRESSED' named entity 'AIM' named entity 'CONCLUDE' named entity 'CONTENT' named entity 'BASAL' named entity 'MALE' named entity 'ADAM17' named entity 'MICE' named entity 'DYNAMICS' named entity 'FAILED' named entity 'PANCREATIC' named entity 'CELLULAR' named entity 'DOES NOT'

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