The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Free Fatty Acid-Induced Inhibition of Glucose and Insulin-Like Growth Factor I-Induced Deoxyribonucleic Acid Synthesis in the Pancreatic β-Cell Line INS-11
Abstract
Pancreatic beta-cell mitogenesis is increased by insulin-like growth factor I (IGF-I) in a glucose-dependent manner. In this study it was found that alternative beta-cell nutrient fuels to glucose, pyruvate, and glutamine/leucine independently induced and provided a platform for IGF-I to induce INS-1 cell DNA synthesis in the absence of serum. In contrast, long chain FFA (>/=C(12)) inhibited 15 mM glucose-induced [(3)H]thymidine incorporation (+/-10 nM IGF-I) by 95% or more within 24 h above 0.2 mM FFA complexed to 1% BSA (K(0.5) for palmitate/1% BSA = 65-85 microM for 24 h; t(0.5) for 0.2 mM palmitate/1% BSA = approximately 6 h). FFA-mediated inhibition of glucose/IGF-I-induced ss-cell DNA synthesis was reversible, and FFA oxidation did not appear to be required, nor did FFA interfere with glucose metabolism in INS-1 cells. An examination of mitogenic signal transduction pathways in INS-1 cells revealed that glucose/IGF-I induction of early signaling elements in SH2-containing protein (Shc)- and insulin receptor substrate-1/2-mediated pathways leading to downstream mitogen-activated protein kinase and phosphoinositol 3'-kinase activation, were unaffected by FFA. However, glucose-/IGF-I-induced activation of protein kinase B (PKB) was significantly inhibited, and protein kinase Czeta was chronically activated by FFA. It is possible that FFA-mediated inhibition of ss-cell mitogenesis contributes to the reduction of beta-cell mass and the subsequent failure to compensate for peripheral insulin resistance in vivo that is key to the pathogenesis of obesity-linked diabetes.
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Cites
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Cited by
Karaskov, E., Scott, C., Zhang, L., Teodoro, T., Ravazzola, M., & Volchuk, A. (2006) · Endocrinology · doi:10.1210/en.2005-1494 · Cited by 573
Chen, P., Torralba, M., Tan, J., Embree, M., Zengler, K., Stärkel, P., van Pijkeren, J.-P., DePew, J., Loomba, R., Ho, S. B., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.09.014 · Cited by 322
POWELL, D. J., TURBAN, S., GRAY, A., HAJDUCH, E., & HUNDAL, H. S. (2004) · Biochemical Journal · doi:10.1042/bj20040139 · Cited by 267
Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport
Ohtsubo, K., Chen, M. Z., Olefsky, J. M., & Marth, J. D. (2011) · Nature Medicine · doi:10.1038/nm.2414 · Cited by 249
Peroxisome Proliferator Activator Receptor γ Coactivator-1 Expression Is Reduced in Obesity
Crunkhorn, S., Dearie, F., Mantzoros, C., Gami, H., da Silva, W. S., Espinoza, D., Faucette, R., Barry, K., Bianco, A. C., & Patti, M. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611214200 · Cited by 236
Metadata
- Authors
- Cousin, S. P., Hügl, S. R., Wrede, C. E., Kajio, H., Myers, M. G., & Rhodes, C. J.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2001-01
- Volume
- 142
- Issue
- 1
- Pages
- 229-240
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2021286587
- Cited by
- 276
- References
- 47
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Free Fatty Acid-Induced Inhibition of Glucose and Insulin-Like Growth Factor I-Induced Deoxyribonucleic Acid Synthesis in the Pancreatic β-Cell Line INS-11. https://app.cochat.ai/papers/10.1210/endo.142.1.7863
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- Cousin, S. P., Hügl, S. R., Wrede, C. E., Kajio, H., Myers, M. G., & Rhodes, C. J. (2001). Free Fatty Acid-Induced Inhibition of Glucose and Insulin-Like Growth Factor I-Induced Deoxyribonucleic Acid Synthesis in the Pancreatic β-Cell Line INS-11. Endocrinology. https://doi.org/10.1210/endo.142.1.7863
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