The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Regulation of PKD by the MAPK p38δ in Insulin Secretion and Glucose Homeostasis
Open accessAbstract
Dysfunction and loss of insulin-producing pancreatic beta cells represent hallmarks of diabetes mellitus. Here, we show that mice lacking the mitogen-activated protein kinase (MAPK) p38delta display improved glucose tolerance due to enhanced insulin secretion from pancreatic beta cells. Deletion of p38delta results in pronounced activation of protein kinase D (PKD), the latter of which we have identified as a pivotal regulator of stimulated insulin exocytosis. p38delta catalyzes an inhibitory phosphorylation of PKD1, thereby attenuating stimulated insulin secretion. In addition, p38delta null mice are protected against high-fat-feeding-induced insulin resistance and oxidative stress-mediated beta cell failure. Inhibition of PKD1 reverses enhanced insulin secretion from p38delta-deficient islets and glucose tolerance in p38delta null mice as well as their susceptibility to oxidative stress. In conclusion, the p38delta-PKD pathway integrates regulation of the insulin secretory capacity and survival of pancreatic beta cells, pointing to a pivotal role for this pathway in the development of overt diabetes mellitus.
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Cites
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
Inflammation, stress, and diabetes
Wellen, K. E., & Hotamisligil, G. S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25102 · Cited by 4,143
A central role for JNK in obesity and insulin resistance
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The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210
Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
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Gautam, D., Han, S.-J., Hamdan, F. F., Jeon, J., Li, B., Li, J. H., Cui, Y., Mears, D., Lu, H., Deng, C., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.009 · Cited by 299 · cited 1×
“Acetylcholine represents the major neurotransmitter of the peripheral parasympathetic nervous system, and its binding on muscarinic acetylcholine receptors located on the pancreatic b cells potentiates secretion of insulin (Gautam et al., 2006).”
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Cited by
Metabolic Signaling in Fuel-Induced Insulin Secretion
Prentki, M., Matschinsky, F. M., & Madiraju, S. R. M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.018 · Cited by 548
Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase
Smith, B. E., Wang, S. L., Jaime-Figueroa, S., Harbin, A., Wang, J., Hamman, B. D., & Crews, C. M. (2019) · Nature Communications · doi:10.1038/s41467-018-08027-7 · Cited by 517
Single-Cell Transcriptomics of the Human Endocrine Pancreas
Wang, Y. J., Schug, J., Won, K.-J., Liu, C., Naji, A., Avrahami, D., Golson, M. L., & Kaestner, K. H. (2016) · Diabetes · doi:10.2337/db16-0405 · Cited by 432
Kinase inhibition in autoimmunity and inflammation
Zarrin, A. A., Bao, K., Lupardus, P., & Vucic, D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0082-8 · Cited by 431
MAPK signalling in cellular metabolism: stress or wellness?
Gehart, H., Kumpf, S., Ittner, A., & Ricci, R. (2010) · EMBO reports · doi:10.1038/embor.2010.160 · Cited by 326
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Metadata
- Authors
- Sumara, G., Formentini, I., Collins, S., Sumara, I., Windak, R., Bodenmiller, B., Ramracheya, R., Caille, D., Jiang, H., Platt, K. A., Meda, P., Aebersold, R., Rorsman, P., & Ricci, R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 136
- Issue
- 2
- Pages
- 235-248
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2140170107
- Cited by
- 244
- References
- 8
- FWCI
- 22.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Sumara, G., Formentini, I., Collins, S., Sumara, I., Windak, R., Bodenmiller, B., Ramracheya, R., Caille, D., Jiang, H., Platt, K. A., Meda, P., Aebersold, R., Rorsman, P., & Ricci, R. (2009). Regulation of PKD by the MAPK p38δ in Insulin Secretion and Glucose Homeostasis. Cell. https://doi.org/10.1016/j.cell.2008.11.018
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