Endocrine Abstracts

Insulin resistance (IR) is a condition where beta cells are producing insulin, sometimes in large amounts, but the peripheral targets develop an inadequate response to the hormone. Classically insulin resistance has been associated with pathologic conditions. However, there is also physiological IR, associated with the last period of pregnancy and in different moments of the development. We have previously characterised a period of physiological IR, around the ablactation period, in male Wistar rats. We have also described insulin resistance in the metabolic syndrome due to 20% sucrose in drinking water in the same animal. The objective of this work was to identify changes in insulin signalling in adipose tissue and skeletal muscle in Wistar, comparing males and females. We observed that at 20 postnatal day (20 pnd) both sexes present glucose intolerance, compared to adult animals. The peripheric response to insulin and the insulin-stimulated glucose-uptake was lower at 20 pnd, compared to adults. At 20 pnd phosphorylation of the threonine 389 site in the kinase P70S6K was higher in adipose tissue than in muscle. Moreover, the phosphorylation of serine 473 site in Akt was more elevated in adipose tissue and lower in the muscle of 20 pnd rats, compared to adults. Interestingly, the phosphorylation of serine 101 site on IRS1 was higher in adipose tissue of males than in females. These observations suggest that over-activation of the kinase P70S6K during development down-regulates the insulin signalling way. In both sexes, but more in males than female rats GH levels are higher than in adults. This fact could also contribute to the insulin resistance at this stage. It is clear from this date that IR shows sexual dimorphism. The adult model of metabolic syndrome also shows an evident sexual dimorphism, being faster more affected males vs females. Sexual hormones could be contributing to this phenomenon, but there are other variations in this type of dimorphism. Supported by: Conacyt CB-253222, PAPIIT UNAM IN210817 y 213114, Mexico.