It is well established that
insulin inhibits liver ketogenesis. However, during
insulin-induced
hypoglycemia (IIH) the release of counterregulatory
hormones could overcome the
insulin effect on ketogenesis. To clarify this question the ketogenic activity in livers from
alloxan-diabetic rats submitted to long-term IIH was investigated. Moreover, liver glycogenolysis, gluconeogensis, ureagenesis and the production of L-
lactate were measured, and its correlation with blood levels of
ketone bodies (KB), L-
lactate,
glucose,
urea and
ammonia was investigated. For this purpose, overnight fasted
alloxan-diabetic rats (DBT group) were compared with control non-diabetic rats (NDBT group). Long-term IIH was obtained with an
intraperitoneal injection of
Detemir insulin (1 U/kg), and KB,
glucose, L-
lactate,
ammonia and
urea were evaluated at 0, 2, 4, 6, 8 or 10 h after
insulin injection. Because IIH was well established two hours after
insulin injection this time was used for liver perfusion experiments. The administration of
Detemir insulin decreased (P < 0.05) blood KB and
glucose levels, but there was an increase in the blood L-
lactate levels and a rebound increase in blood KB during the
glucose recovery phase of IIH. In agreement with these results, the capacity to produce KB from
octanoate was increased in the livers of DBT rats. Moreover, the elevated blood L-
lactate levels in DBT rats could be attributed to the higher (P < 0.05) glycogenolysis when part of
glucose from glycogenolysis enters glycolysis, producing L-
lactate. In contrast, except
glycerol, gluconeogenesis was negligible in the livers of DBT rats. Therefore, during long-term IIH the higher liver ketogenic capacity of DBT rats increased the risk of hyperketonemia. In addition, in spite of the fact that the
insulin injection decreased blood KB, there was a risk of worsening
lactic acidosis.