In ZDF rats, when glucagon and insulin were infused intraportally with the systemic infusion of somatostatin (Fig. 1, protocols 7 and 8), metabolic features of T2DM-OB seen during the basal period, such as hyperinsulinemia, hyperglucagonemia, hyperglycemia, hyperlactatemia, hyperlipidemia, and greater rates of TGO, EGP, and GC compared with that of ZCL rats, were maintained, indicating successful replacement of their endogenous insulin and glucagon by the intraportal infusion of these hormones at the indicated infusion rates. Here, INS is linked to hyperinsulinism.