Gestational diabetes mellitus is defined as diabetes diagnosed in the second or third trimester of pregnancy in patients with no history of diabetes prior to gestation. It is the most common complication of pregnancy. The underlying pathophysiology shares some common features with type 2 diabetes mellitus (T2DM) combining relatively insufficient insulin secretion with increased peripheral insulin resistance. While a certain degree of insulin resistance is the physiological characteristics of the second half of pregnancy, it is significantly more pronounced in patients with gestational diabetes. Adipose tissue dysfunction and subclinical inflammation in obesity are well-described causes of increased insulin resistance in non-pregnant subjects and are often observed in individuals with T2DM. Emerging evidence of altered adipokine expression and local inflammation in adipose tissue in patients with gestational diabetes suggests an important involvement of adipose tissue in its etiopathogenesis. This review aims to summarize current knowledge of adipose tissue dysfunction and its role in the development of gestational diabetes. We specifically focus on the significance of alterations of adipokines and immunocompetent cells number and phenotype in fat. Detailed understanding of the role of adipose tissue in gestational diabetes may provide new insights into its pathophysiology and open new possibilities of its prevention and treatment.
Patrik Šimják, Anna Cinkajzlová, Kateřina Anderlová, Antonín Pařízek, Miloš Mráz, Michal Kršek and Martin Haluzík
Radmila Kancheva, Martin Hill, David Cibula, Helena Včeláková, Lyudmila Kancheva, Jana Vrbíková, Tomáš Fait, Antonín Pařízek and Luboslav Stárka
Pregnanolone isomers (PIs) and their polar conjugates (PICs) modulate ionotropic receptors such as γ-aminobutyric acid or pregnane X receptors. Besides, brain synthesis, PI penetrates the blood–brain barrier. We evaluated the physiological importance of PI respecting the status of sex, menstrual cycle, and pregnancy. Accordingly, circulating levels of allopregnanolone (P3α 5α ), isopregnanolone (P3β 5α ), pregnanolone (P3α 5β ), epipregnanolone (P3β 5β ), their polar conjugates, and related steroids were measured in 15 men (M), 15 women in the follicular phase (F), 16 women in the luteal phase (L), and 30 women in the 36th week of gestation (P) using GC–MS. The steroid levels were similar in M and F, increased about thrice in L and escalated in P (38–410 times compared with F). The PICs were prevalent over the PIs (16–150 times). Higher ratios of 5α-PIC to 5α-PI found in P indicate the more intensive conjugation of 5α-PI during pregnancy. This mechanism probably provides for the elimination of neuroinhibitory P3α 5α in the maternal compartment. Additionally, our result points to a limited sulfation capacity for neuroinhibitory P3α 5β in P. In contrast to the situation in M, F, and L where the P3α 5β C is the most abundant PIC, and P3α 5β is present in minor quantities compared with the P3α 5α , P3α 5β may acquire physiological importance during pregnancy, contributing to the sustaining thereof. On the other hand, the declining formation of P3α 5β may participate in the initiation of parturition, given the relative abundance of the steroid, its potency to suppress the activity of oxytocin-producing cells and its effectiveness in uterine relaxation.