December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Insulin Receptor Signaling is
Author Affiliations & Notes
  • CE N Reiter
    Cellular and Molecular Physiology
    Penn State College of Medicine Hershey PA
  • BB Woo
    Ophthalmology
    Penn State College of Medicine Hershey PA
  • EB Wolpert
    Ophthalmology
    Penn State College of Medicine Hershey PA
  • M Nakamura
    Ophthalmology
    Penn State College of Medicine Hershey PA
  • AJ Barber
    Ophthalmology
    Penn State College of Medicine Hershey PA
  • DA Antonetti
    Cellular and Molecular Physiology
    Penn State College of Medicine Hershey PA
  • TW GardnerPenn State Retina Research Group
    Ophthalmology
    Penn State College of Medicine Hershey PA
  • Footnotes
    Commercial Relationships   C.E.N. Reiter, None; B.B. Woo, None; E.B. Wolpert, None; M. Nakamura, None; A.J. Barber, None; D.A. Antonetti, None; T.W. Gardner, None. Grant Identification: EY12021, JDRF, ADA, FFS
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1318. doi:
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    • Get Citation

      CE N Reiter, BB Woo, EB Wolpert, M Nakamura, AJ Barber, DA Antonetti, TW GardnerPenn State Retina Research Group; Insulin Receptor Signaling is . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1318.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Diabetic retinopathy affects multiple cell types within the retina and impairs both neuronal and vascular cell survival. Previous data suggests that insulin activates the insulin receptor (IR) cascade in retina. This study investigates retinal IR signaling in diabetes. Methods: Sprague-Dawley rats were injected with vehicle or streptozotocin (65 mg/kg) to induce diabetes for 4, 8, and 12 weeks. A subset of diabetic rats from each time point received acute insulin therapy (5U Humulin R/5U Humulin U, Lilly, twice daily) for three days prior to sacrifice. Upon sacrifice, retinas were collected for IR ß subunit phosphotyrosine blotting and kinase activity. Analysis of other insulin receptor mediators include IRS-1, IRS-2, mTOR, p70 S6 kinase, and CREB was also done by Western blotting and immunohistochemistry. Results: After 4 weeks of diabetes, p70 S6 kinase and CREB immunoreactivity was reduced (p<0.05) in all retinal layers and nuclear layers, respectively. mTOR expression increased in the inner layers and the Müller cells. IR ß phosphorylation and expression levels were unchanged. After 12 weeks of diabetes, total IR ß autophosphorylation had declined significantly (p<0.05) without a loss of content. Insulin therapy rescued IR ß phosphorylation. Conclusion: Endogenous IR signaling may be reduced in the retina by diabetes.

Keywords: 388 diabetic retinopathy • 423 growth factors/growth factor receptors • 474 microscopy: light/fluorescence/immunohistochemistry 
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