INS and Impaired glucose tolerance: In this regard, an impaired first phase insulin secretory response was indeed evident in male RT-SAKO mice at this age and was restored by treatment of mice with the GLP-1 receptor agonist Exendin 4, supporting the notion that a specific GLP-1 deficiency was a causal factor in impaired GSIS, reduced circulating insulin concentrations, and impaired glucose tolerance in these mice.