Insulin Signal Transduction is Impaired in the Type 2 Diabetic Retina

Youde Jiang,Hainan Li,Li Liu,Jiemei Wang ,Jena J Steinle

doi:10.33696/diabetes.1.013

Abstract

Rates of type 2 diabetes are reaching epidemic levels. Yet, the tissue specific alterations due to insulin resistance are only recently being investigated. The goal of the present study was to evaluate retinal insulin signal transduction in a common mouse model of type 2 diabetes, the db/db mouse. Retinal lysates from five month old male db/db and db/+ (control) mice were collected and processed for Western blotting or ELISA analyses for insulin receptor, insulin receptor substrate-1 (IRS-1), Akt, tumor necrosis factor alpha (TNFα) and caspase 3 levels. Data demonstrate increased TNFα and IRS-1 phosphorylation on serine 307. This led to decreased Akt phosphorylation on serine 473 and increased cleavage of caspase 3. Taken together, the data suggest dysfunctional insulin signaling in the retina of the db/db mouse. insulin.

Highlights

With increasing rates of obesity, rates of type 2 diabetes and diabetic complications are expected to rise exponentially over the few decades (American Diabetic Association)
We have previously reported that diabetesinduced increases in tumor necrosis factor alpha (TNFα) can cause phosphorylation of insulin receptor substrate 1 (IRS-1) on serine 307, inhibiting normal insulin signal transduction in retinal endothelial cells [1]
As we have shown in the retina from diabetic rats [3], diabetes significantly reduced insulin receptor and Akt phosphorylation in the db/db retina (Figure 1)

Summary

Introduction

With increasing rates of obesity, rates of type 2 diabetes and diabetic complications are expected to rise exponentially over the few decades (American Diabetic Association). A key feature of type 2 diabetes is a resistance to insulin. We have previously reported that diabetesinduced increases in tumor necrosis factor alpha (TNFα) can cause phosphorylation of insulin receptor substrate 1 (IRS-1) on serine 307, inhibiting normal insulin signal transduction in retinal endothelial cells [1]. This increase in TNFα was associated with increased cleavage of caspase 3. We found similar findings in BBZDR/Wor type 2 diabetic rats [2,3]. It was not clear if these findings occurred in type 2 diabetic mouse models

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