THE INFLUENCE OF INSULIN ON METABOLISM OF GLUCOSE, FREE FATTY-ACIDS AND GLYCEROL IN NORMO-CALCEMIC AND HYPOCALCEMIC EWES DURING DIFFERENT REPRODUCTIVE STATES

Metabolic indicators of glucose and lipid metabolism, i.e. glucose tur nover, insulin concentration in plasma, insulin clearance, concentrati ons of non-esterified fatty acids (NEFA), glycerol and potassium were investigated in nine ewes during three reproductive states in order to examine their importance for development of subclinical ketosis. The increase of insulin in plasma was measured after a continuous 60 min i ntravenous infusion of glucose (4.9 mmol.min(-1)). Turnover of glucose and insulin clearance were quantified during a combined euglycemic, h yperinsulinemic clamp. Insulin was consecutively infused in doses of 5 and 10 mU.kg(-1).min(-1) for about 2 1/2 hours, each. Plasma glucose concentration was adjusted to 5.3 to 5.8 mmol.l(-1). The experiments w ere carried out during non-pregnancy and non-lactation, 4 weeks to 3 d ays before lambing and 3 to 4 weeks after lambing, each during normo-a nd hypocalcemia. Hypocalcemia (0.9 to 1.0 mmol Ca2+.l(-1)) was induced by continuous i.v. infusion of a 5 % Na-EDTA solution. Infusion rate was continuously adjusted. -The glucose induced increase in plasma ins ulin concentration was significantly lower during late pregnancy compa red to peak lactation and non-pregnancy (46.3, 62.4 and 128 mU.l(-1), respectively). The insulin clearance during a hyperinsulinemic clamp w ith 5 mU .kg(-1).min(-1) was significantly less during late pregnancy compared to peak lactation and non-pregnancy (3.7, 6.0, 4.8 ml.kg(-1). min(-1), respectively). The concentrations of NEFA and glycerol in pla sma during the infusion of 5 mU insulin.kg(-1).min(-1) were significan tly higher during late pregnancy than during non-pregnancy (NEFA: 0.41 , 0.04 mmol.l(-1); glycerol: 96, 29 mu mol.l(-1), respectively). The r esults showed that insulin responsiveness was significantly reduced in sheep during late pregnancy. The insulin-mediated uptake of glucose b y muscle and fat tissues and the insulin-mediated inhibition of lipoly sis were significantly reduced during late pregnancy compared to non-p regnancy and lactation. The diminished responsiveness of target tissue towards insulin during late pregnancy predisposed the animals for dev elopment of subclinical ketosis. Hypocalcemia exaggerated this situati on by its inhibitory effect on hepatic gluconeogenesis and by enhancin g insulin resistance of target tissues. The factors which are responsi ble for the altered responsiveness of target tissues towards insulin d uring late pregnancy are yet unknown. The potassium concentration in p lasma showed a proportional increase with increase of the energy defic it of the target tissues. This effect could have been exerted by a dec rease in cellular concentration of ATP and a concomitant reduction of the activity of Na+-K+-ATPase. The indicators of glucose and lipid met abolism which were examined in this study showed marked individual var iation, particularly during late pregnancy. The marked changes of thes e indicators with reproductive stages as well as their great variation between individual sheep support the assumption that they are of sign ificance for the development of pregnancy toxemia in sheep.