Calcium sensing receptor in pregnancies complicated by gestational diabetes mellitus

Papadopoulou, Anna; Gole, Evangelia; Moutafi, Antonia C.; Sfikas, C.; Oehrl, Wolf; Samiotaki, Martina; Papadimitriou, Dimitrios T; Papaevagelou, V.; Nicolaidou, Polyxeni

doi:10.1016/j.placenta.2014.05.001

Cited by 9 publications

(4 citation statements)

References 40 publications

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“…Intriguingly, abundant data have demonstrated that activation of CaSR can exacerbate RI/RI [16] and is implicated in the pathogenesis of diabetes mellitus (DM) [17-19]. Intracellular calcium can be released through the binding of calcium to the ECD of CaSR activated G q proteins, stimulated phospholipase C activity, and an increase in intracellular inositol triphosphate 3 level [20, 21].…”

Section: Introductionmentioning

confidence: 99%

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Hu¹,

Tong²,

Xu³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS), and nitroso-redox imbalance. The calcium-sensing receptor (CaSR) is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM). Methods: The bilateral renal arteries and veins of streptozotocin (STZ)-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR) and NPS-2143 (antagonist of CaSR) at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM), and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM), commercial kits, enzyme-linked immunosorbent assay (ELISA), and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

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Section: Introductionmentioning

confidence: 99%

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Hu¹,

Tong²,

Xu³

et al. 2018

Kidney Blood Press Res

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“…Reduced expression of CaSR in placentas derived from women suffering from gestational diabetes mellitus compared with healthy placentas was found. This was associated with lower Ca 2+ levels measured in cord blood of infants from women suffering from gestational diabetes mellitus supporting its role in placental Ca 2+ -transfer (Papadopoulou et al, 2014). In humans, expression of CaSR was found in both villous and extravillous tissue of first trimester and term placentas (Table 1).…”

Section: Placentamentioning

confidence: 75%

The Calcium-Sensing Receptor and the Reproductive System

Ellinger

2016

Front. Physiol.

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Active placental transport of maternal serum calcium (Ca2+) to the offspring is pivotal for proper development of the fetal skeleton as well as various organ systems. Moreover, extracellular Ca2+ levels impact on distinct processes in mammalian reproduction. The calcium-sensing receptor (CaSR) translates changes in extracellular Ca2+-concentrations into cellular reactions. This review summarizes current knowledge on the expression of CaSR and its putative functions in reproductive organs. CaSR was detected in placental cells mediating materno-fetal Ca2+-transport such as the murine intraplacental yolk sac (IPYS) and the human syncytiotrophoblast. As shown in casr knock-out mice, ablation of CaSR downregulates transplacental Ca2+-transport. Receptor expression was reported in human and rat ovarian surface epithelial (ROSE) cells, where CaSR activation stimulates cell proliferation. In follicles of various species a role of CaSR activation in oocyte maturation was suggested. Based on studies in avian follicles, the activation of CaSR expressed in granulosa cells may support the survival of follicles after their selection. CaSR in rat and equine sperms was functionally linked to sperm motility and sperm capacitation. Implantation involves complex interactions between the blastocyst and the uterine epithelium. During early pregnancy, CaSR expression at the implantation site as well as in decidual cells indicates that CaSR is important for blastocyst implantation and decidualization in the rat uterus. Localization of CaSR in human extravillous cytotrophoblasts suggests a role of CaSR in placentation. Overall, evidence for functional involvement of CaSR in physiologic mammalian reproductive processes exists. Moreover, several studies reported altered expression of CaSR in cells of reproductive tissues under pathologic conditions. However, in many tissues we still lack knowledge on physiological ligands activating CaSR, CaSR-linked G-proteins, activated intracellular signaling pathway, and functional relevance of CaSR activation. Clearly, more work is required in the future to decode the complex physiologic and pathophysiologic relationship of CaSR and the mammalian reproductive system.

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“…Transgenic mice with gain-offunction mutation of CaSR have reduced islet mass and b-cell proliferation, as well as hypoinsulinemia and hyperglycemia (108). In human pregnancies complicated by GDM, expression of CaSR was found to be significantly reduced in the placenta, which may have contributed to the hypocalcemia observed in 16% of the newborns (109). Whether CaSR expression was also altered in islets of women with GDM could not be determined due to the inaccessibility of pancreatic tissue for analysis.…”

Section: Calcium and Gestational Diabetesmentioning

confidence: 99%

Beta-Cell Adaptation to Pregnancy – Role of Calcium Dynamics

Pretorius

Huang

2022

Front. Endocrinol.

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During pregnancy, the mother develops insulin resistance to shunt nutrients to the growing fetus. As a result, the maternal islets of Langerhans undergo several changes to increase insulin secretion in order to maintain glucose homeostasis and prevent the development of gestational diabetes. These changes include an increase in β-cell proliferation and β-cell mass, upregulation of insulin synthesis and insulin content, enhanced cell-to-cell communication, and a lowering of the glucose threshold for insulin secretion, all of which resulting in an increase in glucose-stimulated insulin secretion. Emerging data suggests that a change in intracellular calcium dynamics occurs in the β-cell during pregnancy as part of the adaptive process. Influx of calcium into β-cells is crucial in the regulation of glucose-stimulated insulin secretion. Calcium fluxes into and out of the cytosol, endoplasmic reticulum, and mitochondria are also important in controlling β-cell function and survival. Here, we review calcium dynamics in islets in response to pregnancy-induced changes in hormones and signaling molecules, and how these changes may enhance insulin secretion to stave off gestational diabetes.

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Calcium sensing receptor in pregnancies complicated by gestational diabetes mellitus

Cited by 9 publications

References 40 publications

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

The Calcium-Sensing Receptor and the Reproductive System

Beta-Cell Adaptation to Pregnancy – Role of Calcium Dynamics

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