The effect of induced hyperglucagonaemia on the Zucker fatty rat

The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/-). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness.