All these previous studies agreed with our findings that subjecting rats to HFD and STZ injections resulted in hyperinsulinemia (Figure 1), as well as downregulation of the p-PI3K/p-AKT/p-mTOR signaling pathway in the liver (Figure 6), which in turn decreased the sensitivity of IRS-1/IRS-2 (Figure 3), while treatment with pioglitazone and the benzosulfonamide derivative resulted in increasing insulin receptor sensitivity of IRS-1/IRS-2, resulting in an upregulated p-PI3K/p-AKT/p-mTOR signaling pathway, in agreement with the histological results (Figure 7, Figure 8 and Figure 9). This evidence concerns the gene IRS1 and Hyperinsulinemia.