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Review

Insulin, insulin analogues and diabetic retinopathy

, &
Pages 54-62 | Received 24 Oct 2007, Accepted 08 Jan 2008, Published online: 10 Oct 2008
 

Abstract

Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

Abbreviations
Akt=

Proteinkinase beta

AP-1=

activating protein 1

DR=

diabetic retinopathy

FGF-2=

fibroblast growth factor 2

HIF=

Hypoxia-inducible factor

IGF-1=

insulin-like growth factor-1

JNK=

c-Jun N-terminal kinase

NF-kB=

nuclear factor kappa B

rhIGF-1=

recombinant human IGF-1

rh-insulin=

recombinant human insulin

RPE=

retinal pigment epithelium

VEGF=

vascular endothelial growth factor

Abbreviations
Akt=

Proteinkinase beta

AP-1=

activating protein 1

DR=

diabetic retinopathy

FGF-2=

fibroblast growth factor 2

HIF=

Hypoxia-inducible factor

IGF-1=

insulin-like growth factor-1

JNK=

c-Jun N-terminal kinase

NF-kB=

nuclear factor kappa B

rhIGF-1=

recombinant human IGF-1

rh-insulin=

recombinant human insulin

RPE=

retinal pigment epithelium

VEGF=

vascular endothelial growth factor

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