Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic β-cells
Open accessAbstract
Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic β-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. In this study, we analyzed leptin-mediated signal transduction and preproinsulin gene regulation at the molecular level in pancreatic β-cells. Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 β-cells. Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling (SOCS)3 in INS-1 β-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo. Transcriptional activation of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced STAT3 and STAT5b DNA binding to specific promoter regions. Unexpectedly, SOCS3 inhibited both basal and STAT3/5b-dependent rat preproinsulin 1 gene promoter activity in INS-1 cells. These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic β-cells. In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic β-cells.
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SOCS3 blocks STAT3-dependent regulation of the preproinsulin 1 gene promoter.
“whereas SOCS3 blocks the STAT3-dependent regulation of the preproinsulin 1 gene promoter (Laubner et al., 2005).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Laubner et al., 2005
The leptin/JAK2/STAT3 pathway inhibits insulin synthesis.
“The leptin/JAK2/STAT3 pathway inhibits insulin synthesis, whereas SOCS3 blocks the STAT3-dependent regulation of the preproinsulin 1 gene promoter (Laubner et al., 2005).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Laubner et al., 2005
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STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Bates, S. H., Stearns, W. H., Dundon, T. A., Schubert, M., Tso, A. W. K., Wang, Y., Banks, A. S., Lavery, H. J., Haq, A. K., Maratos-Flier, E., et al. (2003) · Nature · doi:10.1038/nature01388 · Cited by 1,010 · cited 1× · see citing works
“Previous studies have identified STAT3 signaling in the hypothalamus as particularly essential for leptin regulation of energy balance (32,33).”
BackgroundRegion-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
Münzberg, H., Flier, J. S., & Bjørbæk, C. (2004) · Endocrinology · doi:10.1210/en.2004-0726 · Cited by 737 · see citing works
Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., Torisu, T., Chien, K. R., Yasukawa, H., & Yoshimura, A. (2004) · Nature Medicine · doi:10.1038/nm1071 · Cited by 651 · see citing works
Seufert, J., Kieffer, T. J., Leech, C. A., Holz, G. G., Moritz, W., Ricordi, C., & Habener, J. F. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.2.5460 · Cited by 278 · see citing works
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- Krebs DL, Hilton DJ: A new role for SOCS in insulin action: suppressor of cytokine signaling (Review). Sci STKE 2003:PE6, 2003
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Stern, J. H., Rutkowski, J. M., & Scherer, P. E. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.011 · Cited by 1,031 · see citing works
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314 · see citing works
“The leptin/JAK2/STAT3 pathway inhibits insulin synthesis, whereas SOCS3 blocks the STAT3-dependent regulation of the preproinsulin 1 gene promoter (Laubner et al., 2005).”
BackgroundPark, H.-K., & Ahima, R. S. (2014) · F1000Prime Reports · doi:10.12703/p6-73 · Cited by 171 · see citing works
Hyperinsulinemia: A cause of obesity?
Erion, K. A., & Corkey, B. E. (2017) · Current Obesity Reports · doi:10.1007/s13679-017-0261-z · Cited by 161 · see citing works
Human β-Cell Proliferation and Intracellular Signaling: Part 3
Stewart, A. F., Hussain, M. A., García-Ocaña, A., Vasavada, R. C., Bhushan, A., Bernal-Mizrachi, E., & Kulkarni, R. N. (2015) · Diabetes · doi:10.2337/db14-1843 · Cited by 142 · see citing works
- Authors
- Laubner, K., Kieffer, T. J., Lam, N. T., Niu, X., Jakob, F., & Seufert, J.
- Affiliations
- University of Würzburg (DE)
- University of British Columbia (CA)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-12-01
- Volume
- 54
- Issue
- 12
- Pages
- 3410-3417
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2128590337
- Cited by
- 85
- References
- 4
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 4 · 2014: 1 · 2013: 10 · 2012: 5
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael Smith Health Research BC
- Deutscher Akademischer Austauschdienst
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, SOCS3, pancreatic beta cells, JAK/STAT signaling, STAT3, STAT5B, transcriptional regulation, insulin secretion, negative feedback regulation, ob/ob mice, INS-1 cells
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, Base Sequence, Gene Expression Regulation, Immunohistochemistry, Insulin, Insulinoma, Islets of Langerhans, Pancreatic Neoplasms, Proinsulin, Protein Precursors, RNA, Messenger, Genes, Reporter, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Leptin, Cell Line, Tumor, STAT3 Transcription Factor, STAT5 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Rats
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