Chronic intermittent hypoxia affects the expression of IRS - 2/p - Akt/GSK - 3 in the liver of SD rats and its impact on glucose metabolism.

Background: Epidemiological studies indicate a strong association between OSA and type 2 diabetes. Currently, the insulin signal transduction pathway and its associated effector proteins have emerged as a focal point in type 2 diabetes research. However, the underlying mechanisms in OSA remain elusive. We have established an experimental model of chronic intermittent hypoxia in SD rats and conducted measurements of their fasting blood glucose, fasting plasma insulin levels, as well as the insulin signaling pathway effector proteins IRS-2, P-Akt, and GSK-3.

Method: In the experiment, the gas path control system connected to a sealed glass container regulated the delivery of oxygen and nitrogen, ensuring a minimum oxygen concentration of 6%-12% within the cabin. Forty male Sprague-Dawley rats were divided into five groups (n = 8) and exposed to chronic intermittent hypoxia or normal air environment for 2, 4, 6, and 8 weeks, respectively. Upon completion of the experiment, the rats were anesthetized and euthanized. Immediately thereafter, their fasting blood glucose was measured, and their fasting insulin levels were determined using radioimmunoassay. Finally, the insulin resistance index (HOMA-IR) was calculated based on the steady-state model evaluation method. HE staining was employed to observe the morpho- logical changes of liver cells in each group of rats. Immunohistochemistry was utilized to detect the expression of insulin signaling pathway-related effector proteins, namely IRS-2, p-Akt, and GSK-3, in the liver, with their expression levels expressed as average grayscale values.

Result: With the extension of intermittent hypoxia exposure duration, compared to the normal control group, the fasting blood glucose, fasting insulin, and insulin resistance index of rats in each experimental group increased (n = 8, P < 0.05). Additionally, the liver cells of rats exhibited damage and morphological changes. The expression of liver pathway proteins IRS-2 and P-Akt decreased (n = 8, P < 0.05), whereas the expression of GSK-3 protein increased (n = 8, P < 0.05).

Conclusion: Chronic intermittent hypoxia activates the proteins IRS-2, P-Akt, and GSK-3 in the hepatic insulin signaling pathway, leading to liver cell damage, insulin resistance, and glucose metabolism disorders.