Suppression of GLUT1; A new strategy to prevent diabetic complications

Lili Lu, Christopher P. Seidel, Takeshi Iwase, Rebecca K. Stevens, Yuan Yuan Gong, Xinyi Wang, Sean F. Hackett, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non-diabetics. 1,9-Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein β2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy.

Original languageEnglish (US)
Pages (from-to)251-257
Number of pages7
JournalJournal of Cellular Physiology
Volume228
Issue number2
DOIs
StatePublished - Feb 2013

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Diabetes Complications
Glucose
Colforsin
Diabetic Retinopathy
Biomarkers
Blood Glucose
Blood
Retina
Intraocular Injections
Crystallins
Facilitative Glucose Transport Proteins
Genistein
Adenylyl Cyclases
Superoxides
Cyclic AMP
Vascular Endothelial Growth Factor A
Brain
Cells
Therapeutics
Erythrocytes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Suppression of GLUT1; A new strategy to prevent diabetic complications. / Lu, Lili; Seidel, Christopher P.; Iwase, Takeshi; Stevens, Rebecca K.; Gong, Yuan Yuan; Wang, Xinyi; Hackett, Sean F.; Campochiaro, Peter A.

In: Journal of Cellular Physiology, Vol. 228, No. 2, 02.2013, p. 251-257.

Research output: Contribution to journalArticle

Lu, L, Seidel, CP, Iwase, T, Stevens, RK, Gong, YY, Wang, X, Hackett, SF & Campochiaro, PA 2013, 'Suppression of GLUT1; A new strategy to prevent diabetic complications', Journal of Cellular Physiology, vol. 228, no. 2, pp. 251-257. https://doi.org/10.1002/jcp.24133
Lu, Lili ; Seidel, Christopher P. ; Iwase, Takeshi ; Stevens, Rebecca K. ; Gong, Yuan Yuan ; Wang, Xinyi ; Hackett, Sean F. ; Campochiaro, Peter A. / Suppression of GLUT1; A new strategy to prevent diabetic complications. In: Journal of Cellular Physiology. 2013 ; Vol. 228, No. 2. pp. 251-257.
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