GLUCONEOGENESIS IN HUMAN PLACENTA: EFFECTS OF INSULIN AND HYPOXIA IN VITRO

The placenta as fetal tissue is subjected to alterations of gluconeogenesis like the newborn itself. We studied tissue of term placentae incubated in amino acid solution with 14.0 mmol glucose /l under gasing with either oxigen or nitrogen. As specific inhibitor of gluconeogenesis 2 mM of 2, 5-anhydro-D-mannitol (AM) was used, human insulin was administered at a final concentration of 180 μU/ml. The glucose utilization (U(gluc)), L-lactate (P(lac)) and pyruyate production (P(pyr)) were calculated after tracing with (U- 14C)glucose and separation by HPLC technique.- RESULTS: 1. U(gluc) was 24.8 % (±1.3 S.D.)(n=9) per g tissue in 120 min. After AM, the glucose consumption was elevated up to 33.3 % (±4.1) (p<0.01)(n=6). Insulin did not significantly influence the elevated U(gluc) in AM conditions.-2. P(lac) was lowered by AM from 18.2 % (±2.4) to 12.9 % (±2.3)(p<0.02)(n=6). Insulin abolished this effict (P(lac) up to 19.8 % (±5.7)).-3. P(pyr) remained unaltered by AM and insulin.-4. In hypoxic conditions with inhibited gluconeogenesis, elevation of U(gluc) from 38.2 %(±2.2) to 44.5 % (±6.7) was observed. Also P(lac) increased to 39.1 % (±6.6). CONCLUSIONS: 1. Blocking of gluconeogenesis elevates the glucose utilization by one third. 2. The lactate production is reduced without gluconeogenesis, but is counteracted by insulin. 3. In, hypoxia, the gluconeogenesis continues to function in placenta. Supported by Deutsche Forschungsgemeinschaft, He 1107/2