The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice
Open accessAbstract
Aim/hypothesis We previously reported that repeated subcutaneous or intracerebroventricular injection of brain-derived neurotrophic factor (BDNF) reduces blood glucose concentrations in obese diabetic C57BL/KsJ-db/db mice. In this study, we assessed the effects of BDNF on insulin action in peripheral tissues of diabetic mice.Methods First, brain-derived neurotrophic factor (20 mg/kg) was subcutaneously given to male db/db mice for 14 days and then the insulin-stimulated tyrosine phosphorylation of insulin receptors and insulin-stimulated phosphatidylinositol (PI) 3-kinase activity in peripheral tissues was assessed. Second, we examined the effects of a single subcutaneous or intracerebroventricular brain-derived neurotrophic factor injection on insulin responsiveness in liver and skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Third, the effects of brain-derived neurothrophic factor on insulin action were also examined in cultured cells.Results Repeated injection of BDNF to db/db mice for 14 days enhanced insulin-stimulated tyrosine phosphorylation of insulin receptors in liver and insulin-stimulated PI 3-kinase activity in liver, skeletal muscle and interscapular brown adipose tissue. We then examined the rapid effect of BDNF on insulin signalling in vivo. A single subcutaneous or intracerebroventricular injection of BDNF rapidly increased insulin-stimulated tyrosine phosphorylation of insulin receptors and PI 3-kinase activity in liver of STZ-mice. No direct effect of brain-derived neurothrophic factor was observed on insulin signalling in primary cultured hepatocytes, L6 muscle cells or 3T3-L1 adipocytes. Brain-derived neurothrophic factor did not affect either glucose uptake or gluconeogenesis in these cells.Conclusion/interpretation These data indicate that brain-derived neurothrophic factor rapidly enhances insulin signal transduction in liver and shows hypoglycaemic action in diabetic mice.
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Cites
Neurotrophic factors: from molecule to man
Lindsay, R. M., Wiegand, S. J., Altar, C. A., & DiStefano, P. S. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90099-x · Cited by 789 · see citing works
Neurotrophic factors and their receptors.
Barbacid, M. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80022-0 · Cited by 577 · see citing works
Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin Receptor
Eck, M. J., Dhe‐Paganon, S., Trüb, T., Nolte, R. T., & Shoelson, S. E. (1996) · Cell · doi:10.1016/s0092-8674(00)81236-2 · Cited by 323 · see citing works
Takayama, S., White, M. F., & Kahn, C. R. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)69090-8 · Cited by 317 · see citing works
Insulin Receptor Deficiency in Genetic and Acquired Obesity
Soli, A. H., Kahn, C. R., Neville, D. M., & Roth, J. (1975) · Journal of Clinical Investigation · doi:10.1172/jci108155 · Cited by 260 · see citing works
Folli, F. B., Saad, M. J. A., Backer, J., & Kahn, C. R. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116768 · Cited by 221 · see citing works
Tonra, J. R., Ono, M., Liu, X., Garcia, K., Jackson, C., Yancopoulos, G. D., Wiegand, S. J., & Wong, V. (1999) · Diabetes · doi:10.2337/diabetes.48.3.588 · Cited by 186 · see citing works
King, P. A., Horton, E. D., Hirshman, M. F., & Horton, E. S. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116025 · Cited by 172 · see citing works
Therapeutic potential of neurotrophic factors for neurological disorders
Yuen, E., & Mobley, W. C. (1996) · Annals of Neurology · doi:10.1002/ana.410400304 · Cited by 138 · see citing works
Physiology of the Neurotrophins
Lewin, G. R. (1996) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.19.1.289 · Cited by 128 · see citing works
Ono, M., Ichihara, J., Nonomura, T., Itakura, Y., Taiji, M., Nakayama, C., & Noguchi, H. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7220 · Cited by 127 · see citing works
Self-citationDefect in skeletal muscle phosphatidylinositol-3-kinase in obese insulin-resistant mice.
Heydrick, S. J., Jullien, D., Gautier, N., Tanti, J., Giorgetti‐Peraldi, S., OBBERGHEN, E. V., & MARCHAND‐BRUSTEL, Y. L. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116337 · Cited by 114 · see citing works
Ono, M., Itakura, Y., Nonomura, T., Nakagawa, T., Nakayama, C., Taiji, M., & Noguchi, H. (2000) · Metabolism · doi:10.1016/s0026-0495(00)90988-0 · Cited by 84 · see citing works
Self-citationThe response of motoneurons to neurotrophins
Sendtner, M., Holtmann, B., & Hughes, R. A. (1996) · Neurochemical Research · doi:10.1007/bf02532307 · Cited by 78 · see citing works
Recent advances in the treatment of neurodegenerative disorders and cognitive dysfunction
(1995) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(95)90079-9 · Cited by 61 · see citing works
Pioglitazone Improves Insulin Signaling Defects in Skeletal Muscle from Wistar Fatty (fa/fa) Rats
Hayakawa, T., Shiraki, T., Morimoto, T., Shii, K., & Ikeda, H. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0912 · Cited by 48 · see citing works
BDNF and NT-3 widen the scope of neurotrophin activity: pharmacological implications
Skup, M. (1994) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-1994-1006 · Cited by 29 · see citing works
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Matthews, V. B., Åström, M.-B., Chan, M. H. S., Bruce, C. R., Krabbe, K. S., Prelovsek, O., Åkerström, T., Yfanti, C., Broholm, C., Mortensen, O. H., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1364-1 · Cited by 722 · see citing works
BDNF mediates adaptive brain and body responses to energetic challenges
Marosi, K., & Mattson, M. P. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.10.006 · Cited by 568 · see citing works
Noble, E. E., Billington, C. J., Kotz, C. M., & Wang, C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00776.2010 · Cited by 284 · see citing works
Cytokines and abnormal glucose and lipid metabolism
Shi, J., Fan, J., Su, Q., & Yang, Z. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00703 · Cited by 282 · see citing works
The role of exercise-induced myokines in regulating metabolism
Huh, J. Y. (2018) · Archives of Pharmacal Research · doi:10.1007/s12272-017-0994-y · Cited by 242 · see citing works
Neurotrophic factor control of satiety and body weight
Xu, B., & Xie, X. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.24 · Cited by 203 · see citing works
Skeletal muscle is an endocrine organ
Iizuka, K., Machida, T., & Hirafuji, M. (2014) · Journal of Pharmacological Sciences · doi:10.1254/jphs.14r02cp · Cited by 189 · see citing works
Jiménez-Maldonado, A., Rentería, I., García-Suárez, P. C., Moncada-Jiménez, J., & Freire-Royes, L. F. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00839 · Cited by 118 · see citing works
Song, H.-D., Kim, S. N., Saha, A., Ahn, S.-Y., Akindehin, S., Son, Y., Cho, Y. K., Kim, M., Park, J.-H., Jung, Y.-S., et al. (2020) · Aging and disease · doi:10.14336/ad.2019.0810 · Cited by 14 · see citing works
- Authors
- Tsuchida, A., Nakagawa, T., Itakura, Y., Ichihara, J., Ogawa, W., Kasuga, M., Taiji, M., & Noguchi, H.
- Affiliations
- Kobe University (JP)
- Venue
- Diabetologia
- Published
- 2001-04-25
- Volume
- 44
- Issue
- 5
- Pages
- 555-566
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2028713882
- Cited by
- 91
- References
- 17
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 7
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- brain-derived neurotrophic factor, insulin signaling, insulin resistance, type 2 diabetes, db/db mice, streptozotocin-induced diabetes, insulin receptor tyrosine phosphorylation, phosphatidylinositol 3-kinase, liver, skeletal muscle, brown adipose tissue, hypoglycemic effect, glucose uptake, gluconeogenesis
- MeSH terms
- Animals, Blood Glucose, Adipose Tissue, Brown, Cell Line, Cerebral Ventricles, Diabetes Mellitus, Experimental, Gluconeogenesis, Glucose, Humans, Injections, Intraventricular, Insulin, Kinetics, Liver, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Receptor, Insulin, Recombinant Proteins, Signal Transduction, 3T3 Cells, Rats, Wistar, Muscle, Skeletal, Brain-Derived Neurotrophic Factor, Phosphatidylinositol 3-Kinases, Hepatocytes, Mice, Rats
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