dc.contributor.author |
Nie, Tina |
|
dc.contributor.author |
Zhang, Shaoping |
|
dc.contributor.author |
Vazhoor Amarsingh, Greeshma |
|
dc.contributor.author |
Liu, Hong |
|
dc.contributor.author |
McCann, Mark J |
|
dc.contributor.author |
Cooper, Garth JS |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2021-07-15T21:36:44Z |
|
dc.date.available |
2021-07-15T21:36:44Z |
|
dc.date.issued |
2019-10-10 |
|
dc.identifier.citation |
Scientific reports 9(1):14588 10 Oct 2019 |
|
dc.identifier.issn |
2045-2322 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/55574 |
|
dc.description.abstract |
Type 2 diabetes mellitus is a major health concern worldwide; however, the molecular mechanism underlying its development is poorly understood. The hormone amylin is postulated to be involved, as human amylin forms amyloid in the pancreases of diabetic patients, and oligomers have been shown to be cytotoxic to β-cells. As rodent amylin is non-amyloidogenic, mice expressing human amylin have been developed to investigate this hypothesis. However, it is not possible to differentiate the effects of amylin overexpression from β-cell loss in these models. We have developed transgenic mice that overexpress [<sup>25, 28, 29</sup> triprolyl]human amylin, a non-amyloidogenic variant of amylin, designated the Line 44 model. This model allows us to investigate the effects of chronic overexpression of non-cytotoxic amylin. We characterised this model and found it developed obesity, hyperglycaemia and hyperinsulinaemia. This phenotype was associated with alterations in the expression of genes involved in the amylin, insulin and leptin signalling pathways within the brain. This included genes such as c-Fos (a marker of amylin activation); Socs3 (a leptin inhibitor); and Cart, Pomc and Npy (neuropeptides that control appetite). We also examined Socs3 protein expression and phosphorylated Stat3 to determine if changes at the mRNA level would be reflected at the protein level. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Science and Business Media LLC |
|
dc.relation.ispartofseries |
Scientific reports |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Brain |
|
dc.subject |
Animals |
|
dc.subject |
Mice, Transgenic |
|
dc.subject |
Humans |
|
dc.subject |
Mice |
|
dc.subject |
Diabetes Mellitus, Type 2 |
|
dc.subject |
Obesity |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Body Weight |
|
dc.subject |
Insulin |
|
dc.subject |
Leptin |
|
dc.subject |
Pro-Opiomelanocortin |
|
dc.subject |
Blood Glucose |
|
dc.subject |
Neuropeptide Y |
|
dc.subject |
Proto-Oncogene Proteins c-fos |
|
dc.subject |
Nerve Tissue Proteins |
|
dc.subject |
RNA, Messenger |
|
dc.subject |
Gene Expression Profiling |
|
dc.subject |
Signal Transduction |
|
dc.subject |
Gene Expression Regulation |
|
dc.subject |
Phosphorylation |
|
dc.subject |
Phenotype |
|
dc.subject |
Male |
|
dc.subject |
STAT3 Transcription Factor |
|
dc.subject |
Islet Amyloid Polypeptide |
|
dc.subject |
Suppressor of Cytokine Signaling 3 Protein |
|
dc.subject |
Animals |
|
dc.subject |
Blood Glucose |
|
dc.subject |
Body Weight |
|
dc.subject |
Brain |
|
dc.subject |
Diabetes Mellitus, Type 2 |
|
dc.subject |
Disease Models, Animal |
|
dc.subject |
Gene Expression Profiling |
|
dc.subject |
Gene Expression Regulation |
|
dc.subject |
Humans |
|
dc.subject |
Insulin |
|
dc.subject |
Islet Amyloid Polypeptide |
|
dc.subject |
Leptin |
|
dc.subject |
Male |
|
dc.subject |
Mice |
|
dc.subject |
Mice, Transgenic |
|
dc.subject |
Nerve Tissue Proteins |
|
dc.subject |
Neuropeptide Y |
|
dc.subject |
Obesity |
|
dc.subject |
Phenotype |
|
dc.subject |
Phosphorylation |
|
dc.subject |
Pro-Opiomelanocortin |
|
dc.subject |
Proto-Oncogene Proteins c-fos |
|
dc.subject |
RNA, Messenger |
|
dc.subject |
STAT3 Transcription Factor |
|
dc.subject |
Signal Transduction |
|
dc.subject |
Suppressor of Cytokine Signaling 3 Protein |
|
dc.subject |
Science & Technology |
|
dc.subject |
Multidisciplinary Sciences |
|
dc.subject |
Science & Technology - Other Topics |
|
dc.subject |
ISLET AMYLOID POLYPEPTIDE |
|
dc.subject |
DIET-INDUCED OBESITY |
|
dc.subject |
BETA-CELL |
|
dc.subject |
FEEDBACK INHIBITION |
|
dc.subject |
FOOD-INTAKE |
|
dc.subject |
LEPTIN RECEPTOR |
|
dc.subject |
HORMONE AMYLIN |
|
dc.subject |
INSULIN ACTION |
|
dc.subject |
MESSENGER-RNA |
|
dc.subject |
POMC NEURONS |
|
dc.subject |
1103 Clinical Sciences |
|
dc.subject |
Biomedical |
|
dc.subject |
Basic Science |
|
dc.subject |
Neurodegenerative |
|
dc.subject |
Diabetes |
|
dc.subject |
Metabolic and Endocrine |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.title |
Altered metabolic gene expression in the brain of a triprolyl-human amylin transgenic mouse model of type 2 diabetes. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41598-019-51088-x |
|
pubs.issue |
1 |
|
pubs.begin-page |
14588 |
|
pubs.volume |
9 |
|
dc.date.updated |
2021-06-21T04:01:32Z |
|
dc.rights.holder |
Copyright: The authors |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/31601900 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
784196 |
|
dc.identifier.eissn |
2045-2322 |
|
dc.identifier.pii |
10.1038/s41598-019-51088-x |
|
pubs.number |
14588 |
|
pubs.online-publication-date |
2019-10-10 |
|