Unique pharmacology of a novel allosteric agonist/sensitizer insulin receptor monoclonal antibody.

•A novel anti-insulin receptor monoclonal antibody (IRAB-A) was identified that has both agonist and sensitizing activities.•IRAB-A increases the receptor's affinity for insulin by binding to an allosteric site and does not compete with insulin.•Mice injected once with IRAB-A show improved glycemia and reduced insulinemia, indicative of enhanced insulin sensitivity.•In diet induced obese mice, the insulin sensitizing effect of IRAB-A appears to depend on the degree of insulin resistance.•Chronic treatment of obese mice showed mixed effects on glucose homeostasis under normal fed or meal challenged conditions.