Glucagon antagonists and methods relating thereto are disclosed. The glucagon antagonists include skyrin and skyrin analogs, and serve to inhibit the stimulation of a glucagon-induced response pathway, such as the adenylate cyclase response pathway or the inositol phosphate response pathway. The glucagon antagonists may be used within therapeutic compositions to treat disease states associate with elevated glucose levels, including diabetes and hyperglycemia. The present invention also discloses a biologically pure culture of ATCC accession number 74200, as well as methods relating to the production of glucagon antagonists by cultivating the same in a nutrient medium and recovering the glucagon antagonist therefrom.