Inhibitory Effect of Insulin Treatment on Apoptosis of Intervertebral Disc Cells in a Streptozotocin-Induced Diabetic Rat Model

Asian Spine J. 2023 Feb;17(1):1-7. doi: 10.31616/asj.2021.0514. Epub 2022 Jun 3.

Abstract

Study design: Experimental study using a streptozotocin (STZ)-induced diabetic rat model.

Purpose: This study aims to investigate whether insulin treatment could attenuate disc cell apoptosis and matrix degradation in a STZ-induced diabetic rat model.

Overview of literature: Diabetes is a significant risk factor for disc degeneration due to excessive apoptosis of disc cells and matrix degradation. However, no studies were noted to demonstrate the inhibitory effect of insulin treatment on the apoptosis of disc cells and matrix degradation in diabetic patients.

Methods: Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs).

Results: Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group.

Conclusions: The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

Keywords: Apoptosis; Diabetes; Disc cells; Inhibitory effect; Insulin treatment.