Control of glucose homeostasis in lactating ewes: use of the alloxan-diabetic/insulin-stabilized ewe to study effects of insulin and growth hormone

Two separate experiments were conducted with alloxan-induced, diabetic ewes. In one study it was found that the diabetes induced by alloxan could be stabilized with exogenous insulin (1.2-1.3 U h-1). Feed intake and milk yield were maintained at normal levels even though a mild hyperglycaemia persisted. Despite this, milk fat content tended to increase, an observation that is consistent with insulin being a key factor in the aetiology of the low-milk-fat syndrome in the ruminant. Interruption of insulin infusion then resumption at 90% of the rate previously required to stabilize the diabetes was followed by marked changes in glucose kinetics. Initially, glucose production increased with little change in glucose utilization. This resulted in an increase in plasma glucose, which remained high even though both glucose production and utilization increased, to be similar on resumption of insulin infusions. It seems that the changed sensitivity to insulin reflects 'up-regulation' of insulin receptors. In a second study, exogenous recombinant bovine growth hormone (rebGH) was administered to insulin-stabilized, diabetic ewes. Immediately after the first injection of rebGH, glucose production increased with little change in glucose utilization, which led to increased plasma glucose. This observation suggests that rebGH was glucogenic. Ultimately, it was necessary to increase the dose of insulin to stabilize plasma glucose and by the fourth day of injection of rebGH, the insulin infusion rate required to stabilize the ewes had doubled from c. 1.5 to c. 3 U h-1. After cessation of injections of rebGH the dose of insulin required to stabilize the ewes decreased. These observations confirm the diabetogenic activity of growth hormone (GH) in the sheep.