A new study published in Cell Reports investigated molecular heterogeneity in hyperglucagonemia. In this study human plasma was screened using high resolution proteomics to identify several glucagon variants. The results showed that among the variants proglucagon 1 61 PG 1 61 appeared to be the most abundant. The observations indicated that PG 1 61 is secreted in subjects with obesity both before and after gastric bypass surgery with protein and fat as the main catalysts for secretion before surgery and glucose after surgery. In addition studies in hepatocytes and in 946 cells demonstrated that PG 1 61 dose dependently increases levels of cyclic adenosine monophosphate cAMP through the glucagon receptor and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. On the other hand in rats PG 1 61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. Hence it was concluded that glucagon variants such as PG 1 61 may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.