Diabetes Case Reports

Abstract

Modulation of Ras GTPase and IRS-1 Activities by Spermine in Type 2 Diabetes: A Study Using Goto Kakizaki Rat Model

Boniface O. Ogar, Azubuike I. Okafor, Kenneth C. Nwachukwu, Bassey A. Inyang, Lukman A. Alli*, Michael P. Okoh*

In this study, we investigated the biochemical relationship between spermine, Ras GTPase activity, Insulin Receptor Substrate-1 and how they possibly affect insulin signaling and blood glucose concentrations using Goto Kakizaki (GK) rats as a model for type 2 diabetes mellitus. Type 2 diabetes mellitus is characterized by impaired insulin signaling and glucose dysregulation. Ras GTPases play a crucial role in regulating downstream signaling pathways, cycling between active GTP-bound and inactive GDP-bound states. GK rats were administered varying doses of spermine (6.25-25.00 mg/kg body weight) for six weeks. Spermine treatment enhanced Ras GTPase activity, associated with elevated Guanine Nucleotide Exchange Factor (GEF) activity and reduced GTPase-Activating Protein (GAP) activity. This upregulation corresponded with increased IRS-1 concentrations and improved glucose regulation. Notably, 25.00 mg/kg body weight spermine reduced blood glucose levels by 21.6% (from 12.40 mmol/L to 9.80 mmol/L) and increased total IRS-1 concentrations. Our findings suggest that spermine modulates Ras GTPase activity and IRS-1 expression, leading to improved insulin signaling and glucose homeostasis. These results highlight Ras GTPase modulation as a potential therapeutic target for improving cellular responsiveness to insulin in type 2 diabetes management.

Published Date: 2026-06-11; Received Date: 2026-05-11