The role of interleukin-1β in glucose metabolism during pregnancy and in gestational diabetes mellitus

Pregnancy leads to adaptations of the maternal metabolism and immune system. Increased levels of steroid hormones induce insulin resistance, leading to a glucose gradient from the mother to the fetus, which is modulated by changes in insulin secretion. The maternal adaptive and innate immune systems are modified to accept the fetus, a semi-allograft.
Gestational diabetes mellitus occurs in genetically predisposed women and is associated with obesity and ageing. It is characterized by a further increase of insulin resistance and insufficient insulin secretion. The immune system of women with gestational diabetes is tilted toward inflammation, e.g. with higher interleukin-1β (IL-1β) expression in the adipose tissues and the placenta, and with higher levels of circulating IL-1β.
We investigated the role of IL-1β in glucose metabolism during pregnancy in young chow-fed mice, and older mice fed high-fat diet. To study the effect of IL-1β, a neutralizing anti-IL-1β antibody and IL-1β-deficient mice were used.
Pregnancy impaired glucose tolerance and increased circulating IL-1β and Il1b gene expression in the uterus of chow-fed mice and of high-fat diet-fed mice compared to their respective non-pregnant controls. Antagonizing IL-1β improved glucose tolerance of pregnant chow-fed mice and of older high-fat diet-fed mice. Similarly, pregnant IL-1β KO mice showed improved glucose tolerance compared to pregnant littermate control mice, supporting the hypothesis that IL-1β plays a role in pregnancy-induced glucose intolerance. Further, antagonizing IL-1β reduced serum levels of several steroid hormones in healthy pregnant mice.
We conclude, that IL-1β contributes to the impairment of glucose metabolism during pregnancy, possibly via modulation of steroid hormones.