E96V Mutation in the Kdelr3 Gene Is Associated with Type 2 Diabetes Susceptibility in Obese NZO Mice
Abstract
:1. Introduction
2. Results
2.1. Heterozygous Carriers of the Nbg15-C3H Alleles Demonstrate Improved Blood Glucose Levels Independently of Their Body Weight
2.2. Introgression of the Nbg15/C3H Locus into the NZO Genome Protects Mice from Chronic Hyperglycemia
2.3. Distal but Not Proximal Nbg15 Sublocus Confers Protection from Hyperglycemia in NZO Congenic Mice
2.4. Distal Nbg15 Sublocus Protects NZO Congenic Mice from Pancreatic Islets Dysfunction
2.5. Kdelr3 Represents a Potentially Causal Gene for the Diabetes-Protective Distal Sublocus
2.6. Changes in Kdelr3 Gene Expression Lead to Alterations in Insulin Granule Maturation and Upregulation of ER Stress Signals in Pancreatic Beta Cells
3. Discussion
Conclusion and Future Perspectives
4. Materials and Methods
4.1. Chemicals and Buffer
4.2. Experimental Animals
4.3. Blood Glucose, Body Weight and Body Composition
4.4. Fasting/Refeeding and Insulin Tolerance Test
4.5. Plasma Insulin
4.6. Pancreas Histology and Islets Isolation
4.7. Cell Culture and Knockdown Experiments
4.8. RNA Extraction, cDNA Synthesis and Quantitative Real-Time PCR
4.9. Sequence, Haplotype and Gene Variants Analysis
4.10. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Altenhofen, D.; Khuong, J.M.-A.; Kuhn, T.; Lebek, S.; Görigk, S.; Kaiser, K.; Binsch, C.; Griess, K.; Knebel, B.; Belgardt, B.-F.; et al. E96V Mutation in the Kdelr3 Gene Is Associated with Type 2 Diabetes Susceptibility in Obese NZO Mice. Int. J. Mol. Sci. 2023, 24, 845. https://doi.org/10.3390/ijms24010845
Altenhofen D, Khuong JM-A, Kuhn T, Lebek S, Görigk S, Kaiser K, Binsch C, Griess K, Knebel B, Belgardt B-F, et al. E96V Mutation in the Kdelr3 Gene Is Associated with Type 2 Diabetes Susceptibility in Obese NZO Mice. International Journal of Molecular Sciences. 2023; 24(1):845. https://doi.org/10.3390/ijms24010845
Chicago/Turabian StyleAltenhofen, Delsi, Jenny Minh-An Khuong, Tanja Kuhn, Sandra Lebek, Sarah Görigk, Katharina Kaiser, Christian Binsch, Kerstin Griess, Birgit Knebel, Bengt-Frederik Belgardt, and et al. 2023. "E96V Mutation in the Kdelr3 Gene Is Associated with Type 2 Diabetes Susceptibility in Obese NZO Mice" International Journal of Molecular Sciences 24, no. 1: 845. https://doi.org/10.3390/ijms24010845