Growth hormone (GH) has an important function in regulating post-natal growth, metabolism, and lifespan and its aberrant signalling has been shown to promote cancer and diabetes. GH acts as an insulin antagonist with elevated insulin sensitivity evident in humans and mice lacking a functional GH receptor (GHR). By utilising a panel of mice possessing specific deletions of GHR signalling pathway we have identified that insulin sensitivity and glucose disappearance rate were enhanced in the muscle and adipose tissue of mice lacking the ability to activate STAT5 via the GHR (Ghr-391-/-) as for GHR null mice (Ghr-/-). These changes were associated with a striking inhibition of hepatic glucose output associated with altered glycogen metabolism and elevated fasting hepatic glycogen content. The enhanced hepatic insulin sensitivity was associated with increased insulin receptor β and IRS1 activation along with activated downstream AKT signalling cascades. While Pck1 expression was unchanged, its inhibitory acetylation was elevated due to decreased SIRT2 expression thereby promoting loss of PCK1. Loss of GH-STAT5 signalling to hepatic ChIP targets would further increase lipogenesis, supporting hepatosteatosis while lowering glucose output. Finally, upregulation of IL-15 expression in muscle, with increased secretion of adiponectin and FGF1 from adipose tissue further promoted this insulin sensitivity. While the insulin sensitivity was also evident in female mouse, the lifespan extension in Ghr mouse models was sexually dimorphic. However, in mice with targeted GHR-JAK-STAT disruption (GHR Box1-motif disruption), allowing Src but not JAK2 activation, life extension was evident in both genders. Our study does not support a universal role for IGF1-deficiency and insulin sensitivity in longevity but indicates towards gender-independent effect of GH-induced Src signalling in promoting longevity.