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Impaired Processing of Prohormones in Secretogranin III-Null Mice Causes Maladaptation to an Inadequate Diet and Stress.

Endocrinology | 2018

Secretogranin III (SgIII), a member of the granin family, binds both to another granin, chromogranin A (CgA), and to a cholesterol-rich membrane that is destined for secretory granules (SGs). The knockdown of SgIII in adrenocorticotropic hormone (ACTH)-producing AtT-20 cells largely impairs the regulated secretion of CgA and ACTH. To clarify the physiological roles of SgIII in vivo, we analyzed hormone secretion and SG biogenesis in newly established SgIII-knockout (KO) mice. Although the SgIII-KO mice were viable and fertile and exhibited no overt abnormalities under ordinary rearing conditions, a high-fat/high-sucrose diet caused pronounced obesity in the mice. Furthermore, in the SgIII-KO mice compared with wild-type (WT) mice, the stimulated secretion of active insulin decreased substantially, whereas the storage of proinsulin increased in the islets. The plasma ACTH was also less elevated in the SgIII-KO mice than in the WT mice after chronic restraint stress, whereas the storage level of the precursor proopiomelanocortin in the pituitary gland was somewhat increased. These findings suggest that the lack of SgIII causes maladaptation of endocrine cells to an inadequate diet and stress by impairing the proteolytic conversion of prohormones in SGs, whereas SG biogenesis and the basal secretion of peptide hormones under ordinary conditions are ensured by the compensatory upregulation of other residual granins or factors.

Pubmed ID: 29281094 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


Anti-Prohormone Convertase PC1/PC3 (antibody)

RRID:AB_1977441

This polyclonal targets Prohormone Convertase PC1/PC3

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PC2 (H-68) (antibody)

RRID:AB_2267765

This polyclonal targets PCSK2

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Carboxypeptidase E (antibody)

RRID:AB_398082

This monoclonal targets Carboxypeptidase E

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Anti Chromogranin A (94-130) (RAT) serum (antibody)

RRID:AB_2716631

This polyclonal targets Chromogranin A

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anti human C-peptide (antibody)

RRID:AB_2716634

This polyclonal targets C-peptide

View all literature mentions

SgII-#23 (antibody)

RRID:AB_2716641

This polyclonal targets secretogranin II

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SgIII-C6 (antibody)

RRID:AB_2716633

This polyclonal targets Secretogranin III

View all literature mentions

SgIII-N#1 (antibody)

RRID:AB_2716632

This polyclonal targets Secretogranin III

View all literature mentions

Anti-Prohormone Convertase PC1/PC3 (antibody)

RRID:AB_1977441

This polyclonal targets Prohormone Convertase PC1/PC3

View all literature mentions