Hypoglycemic episodes exacerbate skeletal muscle insulin resistance in type 2 diabetes mellitus

To date, the specific impact of hypoglycemia on insulin resistance in skeletal muscle is unclear. This study aimed to investigate the correlation between hypoglycemia in individuals with Type 2 Diabetes Mellitus by assessing peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and Akt levels in both skeletal muscle tissue and blood plasma. A true experimental-design study was conducted at the Laboratory of Animal Clinical Study, Faculty of Veterinary, Universitas Syiah Kuala, from October to December 2022. The study utilized 24 male rats (<i>Rattus norvegicus</i>) and the rates were categorized into the following groups: control (K1), streptozocin-induced diabetic without hypoglycemia (K2), streptozocin-induced diabetic with mild hypoglycemia (K3), and streptozocin-induced diabetic with severe hypoglycemia (K4). The rats were euthanized a minimum of 30 min after hypoglycemia was confirmed. W Quadriceps femoris muscle and 2 ml of heart blood were collected. PGC-1α and protein kinase B/Akt were examined using enzyme-linked immunosorbent assay. This study demonstrates that PGC-1α and Akt levels in skeletal muscle and plasma are influenced by hypoglycemia severity in rats, with lower levels associated with more severe hypoglycemia, though no significant differences were observed between mild and severe hypoglycemia groups. A positive correlation was found between PGC-1α and Akt levels in skeletal muscle and plasma, suggesting interdependency. Control group plasma levels were 2.48 ± 0.53 ng/ml for PGC-1α and 11.26 ± 1.21 ng/ml for Akt. Even mild episodes of hypoglycemia can lead to a substantial deterioration of insulin resistance in skeletal muscle.