Effects of Psyllium Husk on Metabolic Regulators, Insulin Resistance, and SIRT6 in Liver and Muscle of Type 2 Diabetic Rats

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder marked by insulin resistance, impaired insulin secretion, oxidative stress, and dysregulated appetite and energy balance. Biomarkers like glucose transporter type 4 (GLUT4), phosphoinositide 3-kinase (PI3K), sirtuin 6 (SIRT6), nesfatin-1, glucagon-like peptide 1 (GLP-1), leptin, and insulin-like growth factor 1 (IGF-1) play important roles in various physiological processes. OBJECTIVES: This study evaluated the metabolic and molecular effects of psyllium in an experimental T2DM rat model. METHODS: Thirty male Wistar Albino rats were divided into three groups (n = 10): Control, Diabetes, and Diabetes + PHP. T2DM was induced by a high-fat diet followed by streptozotocin (35 mg/kg), and the Diabetes + PHP group received 10% PHP from week five. At study completion, metabolic parameters, serum biomarkers, and tissue protein expressions were assessed. RESULTS: T2DM is typically associated with elevated insulin levels and overeating behaviour due to insulin resistance. However, PHP treatment appears to improve insulin sensitivity, leading to a reduction in both body weight and insulin levels. In the T2DM rat model, PHP significantly reduced serum glucose, triglyceride, and leptin levels compared with the diabetic group (p < 0.05). PHP reduced body weight and serum Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulin, total cholesterol, creatinine, C-peptide, and total oxidant status, while increasing serum SIRT6, total antioxidant status, Homeostatic Model Assessment of β-cell function (HOMA-β), nesfatin-1, glucagon-like peptide-1 (GLP-1), and insulin-like growth factor-1 (IGF-1); however, these changes were not statistically significant (p > 0.05). Tissue analyses showed that PHP improved some muscle parameters (triglycerides and total protein; p < 0.05) but did not fully normalise glucose levels in liver and muscle. Uric acid levels remained decreased in liver and muscle after PHP treatment. PHP tended to increase tissue insulin levels while reducing serum insulin, and partially modulated SIRT6 levels, without statistical significance. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed distinct group-specific protein expression patterns in liver and muscle tissues. Additionally, GLUT4, PI3K, and SIRT6 expressions were reduced in diabetic rats and partially restored by PHP without reaching control levels. CONCLUSIONS: PHP demonstrated significant beneficial effects by partially improving metabolic dysfunctions and increasing antioxidant capacity in T2DM. These findings suggest that PHP may be a promising adjunctive therapeutic strategy for managing T2DM-related abnormalities, potentially improving both insulin sensitivity and overall metabolic balance.