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| Status |
Public on Sep 06, 2021 |
| Title |
CaMKIIdelta is required for diabetic hyperglycemia but not nephropathy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Type 2 diabetes is an increasing pandemic health problem and leads to several late diabetic complications of organs including kidney and eye. Lowering elevated blood glucose levels is the typical therapeutic goal in clinical medicine. However, it is possible that hyperglycemia is only a symptom of diabetes but not the correct target to monitor, in order to prevent late diabetic complications. Instead, other diabetes-related alterations could be primary causes for late diabetic complications. Here, we studied the role of CaM Kinase II δ (CaMKIIδ) that is activated through diabetic metabolism. CaMKIIδ is expressed ubiquitously and might therefore affect several different organ systems. We crossed diabetic leptin receptor mutant mice to mice lacking CaMKIIδ globally. Remarkably, CaMKIIδ-deficient diabetic mice did not develop hyperglycemia. As potential underlying mechanisms, we found evidence for improved insulin sensing and increased glucose transport into skeletal muscle. Despite normoglycemia CaMKIIδ-deficient diabetic mice developed the full picture of diabetic nephropathy. In contrast, diabetic retinopathy was prevented. These data challenge the clinical concept of normalizing elevated high glucose levels in diabetes as a causative treatment strategy for late diabetic complications and call for a more detailed analysis of intracellular metabolites in different organs.
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| Overall design |
Retinal ("R") and renal ("K") mRNA profiles of 16week old Lepr(+/+) or Lepr(db/db) with a global CAMK2D knockout (4 groups per organ: WT_ndb; WT_db; KO_ndb; KO_db
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| Contributor(s) |
Chen J, Backs J, Hagenmüller M, Sticht C |
| Citation(s) |
33239449 |
| Submission date |
Sep 09, 2020 |
| Last update date |
Sep 08, 2021 |
| Contact name |
Carsten Sticht |
| Organization name |
University Heidelberg
|
| Department |
ZMF
|
| Street address |
Theodor-Kutzer-Ufer
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| City |
Mannheim |
| ZIP/Postal code |
68169 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA662598 |
| SRA |
SRP281889 |
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