The insulin-resistant obese fa/fa rat is a convenient model in which to study a potential effect of metformin, a biguanide used in the treatment of non-insulin-dependent diabetes, on insulin-mediated glucose utilization. Female fa/fa rats were given metformin orally for 8 days. Studies were performed on anaesthetized post-absorptive rats 5 h after the last dose of metformin. Glucose production and utilization were enhanced 1.5-fold in metformin-treated rats. The enhanced glucose production was almost entirely due to increased glucose recycling. The digestive tract was the only tissue responsible for the enhanced glucose utilization.

The activities and mRNA concentrations of two lipogenic enzymes, fatty acid synthetase and acetyl-CoA carboxylase, and one enzyme involved in glyceroneogenesis, phosphoenolpyruvate carboxykinase (PEPCK), were measured in rat white adipose tissue during the suckling-weaning transition. Activities and mRNA concentrations of lipogenic enzymes were low in suckling rats, whereas activity and mRNA concentration of PEPCK were high. At weaning to a high-carbohydrate diet, the rapid increase in lipogenic enzymes mRNA (10- to 20-fold) and decrease in PEPCK mRNA (10-fold) were followed by parallel changes in enzyme activities. In contrast, weaning to a high-fat diet prevented these modifications. Force feeding suckling rats with carbohydrates induced a rise in blood glucose and plasma insulin concentrations. During these experiments, mRNA concentrations increased 10- to 20-fold for lipogenic enzymes and decreased 5-fold for PEPCK in less than 6 h, whereas all enzyme activities did not vary. This suggests a pretranslational regulation of gene expression. Force feeding suckling rats with a mixture of fat devoid of carbohydrate induced a slight increase in plasma insulin concentration and a fall in PEPCK mRNA but was not accompanied by a rise in lipogenic enzyme mRNAs. This suggested that insulin is a prime regulator of PEPCK gene expression, whereas glucose and insulin act synergistically in the regulation of lipogenic enzyme gene expression.

Food intake was measured at regular intervals over 24 h in pregnant and non-pregnant female rats fed diets of different protein content: 10, 16 and 32%. During the course of pregnancy, a first period of hyperphagia was observed (days 2–12) irrespective of the composition of the diet. A second phase of hyperphagia occurred later (days 16–19) which was more marked with the better balanced diet (16% protein). During the first half of pregnancy, the increase in intake occurred principally at the beginning of the night (compensatory reaction). Later on, the stimulation extended to the last part of the night (anticipatory reaction). The nocturnal predominance of feeding activity was maintained in pregnant females in spite of their increased metabolic requirements.

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