Effect of Hypocalcaemia on Glucose Metabolism in Hyperketonaemic Piglets

Abstract

In nine 2- to 3-month-old hyperketonaemic piglets the kinetics of glucose and D-beta-hydroxybutyrate (D-BHB) metabolism were studied during hypo- and normocalcaemia in paired experiments. Hyperketonaemia (1.3 and 2.5 mmol D-BHB (l plasma)-1) was generated by a stepwise increase of DL-BHB infusion. Hypocalcaemia spontaneously developed in five piglets due to an inherited calcitriol deficiency and was induced in four control piglets by a continuous infusion of Na2-EDTA. The method of single isotopic marker injections of glucose and D-BHB was used to calculate replacement rates, rate constants and half-lives of glucose and D-BHB in plasma. When DL-BHB was infused at the same rate into normo- and hypocalcaemic piglets, hypocalcaemia reduced the rate constant of glucose by 20-30% and the replacement rate of glucose by 34%. In the presence of hyperketonaemia, hypocalcaemia increased the rate of replacement of D-BHB by 6-40%. The replacement rate represents the sum of endogenous production and the rate of DL-BHB infusion. This observation shows that the endogenous production of D-BHB was higher during hypocalcaemia than during normocalcaemia.

Hypocalcemia Reduces Endogenous Glucose Production in Hyperketonemic Sheep

“…The possible reasons for this adaptive response of the pregnant ewes have been discussed in the previous section. These observations are in agreement with results from our own previous studies which showed that glucose flux into peripheral tissues was decreased in hyperketonemic hypocalcemic piglets (Schlumbohm and Harmeyer, 1999). We conclude from these results that hypocalcemia exerts an extraregulatory strain upon the pregnant ewe.…”

“…It was purchased from Du-Pont de Nemours (Dreieich, Germany). Na-DL-βhydroxybutyrate was synthesized as described pre- viously (Schlumbohm and Harmeyer, 1999). The chemicals used for determination of the fraction of the D-βhydroxybutyrate (D-BHB) isomer in the DL-racemate, were the same as described previously (Schlumbohm and Harmeyer, accepted).…”

“…Turnover of glucose was calculated by a noncompartmental approach as described by Shipley and Clark (1972) and modified by Schlumbohm and Harmeyer (1999). The calculation consisted of two steps.…”

“…In fact, from epidemiological studies it was suggested that lactating cows with low plasma Ca concentrations more often develop bovine ketosis than animals with normal calcium concentrations (Bendixen et al, 1987). Our own previous experiments with hypocalcemic hyperketonemic piglets showed for the first time that hypocalcemia depressed endogenous glucose production (Schlumbohm and Harmeyer, 1999). Based on these results we were interested to see whether a similar depressive effect of hypocalcemia on glucose production is also present in sheep and may play a role in the development of pregnancy toxemia.…”

“…Previous experiments have shown that elevated ketone body concentrations in the plasma of sheep reduced endogenous glucose production by approximately 30% (Schlumbohm and Harmeyer, accepted). Furthermore, it was demonstrated in pigs with inherited hypocalcemia that a low plasma calcium concentration exerted an additional depressive effect on endogenous glucose production in the presence of hyperketonemia (Schlumbohm and Harmeyer, 1999). A low plasma calcium concentration (Twardock et al, 1973;Henze et al, 1994) accompanied by an elevated concentration of ketone bodies may also be observed in sheep during late pregnancy.…”