Role of Serotonin (5-HT) in GDM Prediction Considering Islet and Liver Interplay in Prediabetic Mice during Gestation

Pfeifer, Melissa Asuaje; Liebmann, Moritz; Beuerle, Till; Grupe, Katharina; Scherneck, Stephan

doi:10.3390/ijms23126434

Cited by 6 publications

(5 citation statements)

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“…Moreover, an inhibitory effect of high 5-HT concentrations on glucose-stimulated insulin secretion, as well as on glucagon secretion, can be observed in this mouse strain. The increased 5-HT content in β-cells and the resulting paracrine inhibition of α-cells may account for the enhanced hyperglucagonemia during gestation [ 86 ]. In addition to the influences of 5-HT, 17β-estradiol (E2) was shown to be a modulator of glucose-stimulated insulin secretion.…”

Section: The New Zealand Obese (Nzo) Mouse—a Model Of a Common Subpop...mentioning

confidence: 99%

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Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls

Grupe

Scherneck

2023

IJMS

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Gestational diabetes mellitus (GDM) is currently the most common complication of pregnancy and is defined as a glucose intolerance disorder with recognition during pregnancy. GDM is considered a uniform group of patients in conventional guidelines. In recent years, evidence of the disease’s heterogeneity has led to a growing understanding of the value of dividing patients into different subpopulations. Furthermore, in view of the increasing incidence of hyperglycemia outside pregnancy, it is likely that many cases diagnosed as GDM are in fact patients with undiagnosed pre-pregnancy impaired glucose tolerance (IGT). Experimental models contribute significantly to the understanding of the pathogenesis of GDM and numerous animal models have been described in the literature. The aim of this review is to provide an overview of the existing mouse models of GDM, in particular those that have been obtained by genetic manipulation. However, these commonly used models have certain limitations in the study of the pathogenesis of GDM and cannot fully describe the heterogeneous spectrum of this polygenic disease. The polygenic New Zealand obese (NZO) mouse is introduced as a recently emerged model of a subpopulation of GDM. Although this strain lacks conventional GDM, it exhibits prediabetes and an IGT both preconceptionally and during gestation. In addition, it should be emphasized that the choice of an appropriate control strain is of great importance in metabolic studies. The commonly used control strain C57BL/6N, which exhibits IGT during gestation, is discussed in this review as a potential model of GDM.

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Section: The New Zealand Obese (Nzo) Mouse—a Model Of a Common Subpop...mentioning

confidence: 99%

“…Moreover, 5-HT decreased hepatic glucose uptake as well as the glycogen content. In conclusion, 5-HT has a deteriorating effect on hepatic glucose metabolism in NZO mice [ 86 ].…”

Section: The New Zealand Obese (Nzo) Mouse—a Model Of a Common Subpop...mentioning

confidence: 99%

Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls

Grupe

Scherneck

2023

IJMS

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“…Treatment with a serotonin receptor antagonist reduced the 5-HT-mediated deterioration in metabolic status. These data indicate that 5-HT is a potential indicator of GDM in mice before conception [65]. Since serotonin is a precursor to melatonin, dissonance arises again.…”

Section: Aimmentioning

confidence: 74%

Gestational diabetus mellitus and its complications, role of desynchronosis in pathogenesis (a review)

Khara,

Korda,

Podilska

2023

Patologìâ

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Diabetes mellitus is the most common metabolic disorder during pregnancy. The International Diabetes Federation estimates that one in six pregnant women (16.8 %) has diabetes. The prevalence of this disease in the human population is striking and, according to various sources, accounts for 14–25 % of all pregnant women. Most cases of hyperglycemia during pregnancy (75–90 %) is due to gestational diabetes mellitus (GDM). Risk factors, etiology and pathophysiology of GDM are being actively studied, but there are still some controversial issues. For example, the development of GDM in the aspect of circadian rhythm disorders. This problem is especially relevant in connection with pregnancy. After all, there is a two-way relationship here – circadian rhythm disorders affect the course of pregnancy, and pregnancy can be the cause of these disorders. In addition, this problem is relevant for women with a history of endocrine disorders, including diabetes mellitus, as there is a clear link between circadian rhythms and the production of hormones, including insulin. The aim of this review was to show the relationship between the development of GDM, its complications, and circadian rhythm disorders in women. Pregnancy complicated by GDM can have a negative effect on the myocardium and liver. Moreover, this disease has a significant impact on the myocardium of the offspring. GDM also can cause other complications for the mother’s health and fetus or newborn. Scientists have identified a fairly significant number of risk factors for GDM. However, circadian rhythm disorders accompanying pregnancy are often underestimated as a risk factor. In general, there are many controversies regarding the relationship between long / short sleep duration and quality and the risk of developing diabetes, as well as how melatonin and its precursor serotonin affect metabolism in critical organs. Thus, the role of circadian rhythm disorders in the development of diabetes and its consequences is not yet fully understood. It is likely that solving the problem of circadian rhythm disorders will be the key to overcoming a significant proportion of cases of GDM. Therefore, there is an urgent need for further, larger-scale studies to investigate the causal links between circadian rhythm disorders, diabetes mellitus, and pregnancy.

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“…We could not measure ceramides or sulfatides, sphingolipid fractions that are modulated by PPARα and appear to be associated with diabetes [ 102 ]. Additionally, the preIGT phenotype could be a consequence of altered sensitivities to hormone stimuli in pregnancy, as well as epigenetic alterations in DNA methylation patterns, which should be further assessed [ 103 – 105 ]. It is also important to point out interspecies differences, as mice generally have tenfold higher hepatic Pparα gene expression than humans [ 106 , 107 ].…”

Section: Discussionmentioning

confidence: 99%

Differences in lipid metabolism in acquired versus preexisting glucose intolerance during gestation: role of free fatty acids and sphingosine-1-phosphate

et al. 2022

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Background The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. There is increasing evidence that GDM is a heterogeneous disease with different subtypes. An important question in this context is whether impaired glucose tolerance (IGT), which is a typical feature of the disease, may already be present before pregnancy and manifestation of the disease. The latter type resembles in its clinical manifestation prediabetes that has not yet manifested as type 2 diabetes (T2DM). Altered lipid metabolism plays a crucial role in the disorder's pathophysiology. The aim was to investigate the role of lipids which are relevant in diabetes-like phenotypes in these both models with different time of initial onset of IGT. Methods Two rodent models reflecting different characteristics of human GDM were used to characterize changes in lipid metabolism occurring during gestation. Since the New Zealand obese (NZO)-mice already exhibit IGT before and during gestation, they served as a subtype model for GDM with preexisting IGT (preIGT) and were compared with C57BL/6 N mice with transient IGT acquired during gestation (aqIGT). While the latter model does not develop manifest diabetes even under metabolic stress conditions, the NZO mouse is prone to severe disease progression later in life. Metabolically healthy Naval Medical Research Institute (NMRI) mice served as controls. Results In contrast to the aqIGT model, preIGT mice showed hyperlipidemia during gestation with elevated free fatty acids (FFA), triglycerides (TG), and increased atherogenic index. Interestingly, sphingomyelin (SM) concentrations in the liver decreased during gestation concomitantly with an increase in the sphingosine-1-phosphate (S1P) concentration in plasma. Further, preIGT mice showed impaired hepatic weight adjustment and alterations in hepatic FFA metabolism during gestation. This was accompanied by decreased expression of peroxisome proliferator-activated receptor alpha (PPARα) and lack of translocation of fatty acid translocase (FAT/CD36) to the hepatocellular plasma membrane. Conclusion The preIGT model showed impaired lipid metabolism both in plasma and liver, as well as features of insulin resistance consistent with increased S1P concentrations, and in these characteristics, the preIGT model differs from the common GDM subtype with aqIGT. Thus, concomitantly elevated plasma FFA and S1P concentrations, in addition to general shifts in sphingolipid fractions, could be an interesting signal that the metabolic disorder existed before gestation and that future pregnancies require more intensive monitoring to avoid complications. Graphical Abstract This graphical abstract was created with BioRender.com.

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Role of Serotonin (5-HT) in GDM Prediction Considering Islet and Liver Interplay in Prediabetic Mice during Gestation

Cited by 6 publications

References 84 publications

Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls

Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls

Gestational diabetus mellitus and its complications, role of desynchronosis in pathogenesis (a review)

Differences in lipid metabolism in acquired versus preexisting glucose intolerance during gestation: role of free fatty acids and sphingosine-1-phosphate

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