Activity of the calcium-sensing receptor influences blood glucose and insulin levels in rats

Rybczyńska, Apolonia; Marchwińska, Aleksandra; Dyś, Aleksandra; Boblewski, Konrad; Lehmann, Artur; Lewko, Barbara

doi:10.1016/j.pharep.2017.01.034

Cited by 10 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments performed on pancreatic β-cells in vitro show that activation of calcium receptor by calcimimetic R-568 increases insulin secretion, which is due to enhanced release of Ca 2+ from intracellular storages and increased cytoplasmic Ca 2+ concentration (19). Our recently published in vivo experiments confirmed the hypothesis that modulation of CaR activity may also participate in the mechanisms that mediate insulin secretion since the administration of R-568, an agonist of CaR increased insulin level in rats whereas CaR antagonist, NPS2143, had the opposite effect (20). Furthermore, calcium channel blockade by verapamil may prevent changes in blood glucose and insulininduced by CaR activation in rats (21).…”

supporting

confidence: 52%

See 1 more Smart Citation

Diazoxide-induced hyperglycemia in rats is regulated by modulation of calcium receptor activity

Szczoczarz¹,

Szafrański²,

Boblewski³

et al. 2020

Acta Poloniae Pharmaceutica - Drug Research

Self Cite

View full text Add to dashboard Cite

The mechanism of insulin secretion by pancreatic β-cells includes closure of the K ATP channels, depolarization of plasma membrane and stimulation of the Ca 2+ influx. The increase of intracellular Ca 2+ may also be induced by activation of the phospholipase C (PLC)-coupled calcium receptor (CaR) that is present in pancreatic islets. Diazoxide increases blood glucose concentration by inhibiting pancreatic insulin secretion. The mechanism of action of diazoxide involves opening of K ATP channels, cell membrane hyperpolarization, and inhibition of Ca 2+ influx into the cells. The present study was designated to determine the in vivo effects of CaR activation by R-568 and CaR inhibition by NPS 2143 on plasma glucose and insulin levels in the presence of diazoxide. Wistar rats, after 14 h fasting, were anesthetized with inactin and loaded ip with diazoxide 40 mg/kg b.w.. R-568 and NPS2143 were given iv in doses 1 and 2 mg/kg b.w., respectively. Blood glucose, Ca 2+ and insulin levels were determined in selected time points while blood pressure was continuously monitored during the experiment. Diazoxide significantly increased blood glucose level in all tested groups. However, as compared to the rats receiving diazoxide alone, glucose concentration was lower in diazoxide/R-568 group, whereas markedly higher in diazoxide/NPS2143 group. Adversely, insulin level was higher in diazoxide/R-568 and lower in diazoxide /NPS2143 rats, than in animals given diazoxide alone. These results highlight the importance of CaR activity in diazoxide-induced hyperglycemia and hypoinsulinemia.

show abstract

supporting

confidence: 52%

“…ing blood glucose concentrations. Furthermore, we indicated that inhibition of the CaR by calcilytic NPS2143 provoked the opposite effects (20). Used in our experiments diazoxide increases blood glucose concentration by inhibiting pancreatic insulin secretion.…”

mentioning

confidence: 65%

Diazoxide-induced hyperglycemia in rats is regulated by modulation of calcium receptor activity

Szczoczarz¹,

Szafrański²,

Boblewski³

et al. 2020

Acta Poloniae Pharmaceutica - Drug Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Marquis et al showed that NPS2143 had a good specificity with only a few additional targets like monoamine transporters [ 36 ], which may lead in minor side effects. It was recently tested for osteoporosis treatment and calcium hemeostasis related diseases [ 37 – 39 ], and in vivo has demonstrated a good biocompatibility [ 40 , 41 ]. Thus, RCC patients with bone metastases and increased CaSR expression might benefit from a therapy with antagonists like NPS2143, justifying further preclinical and clinical development.…”

Section: Discussionmentioning

confidence: 99%

Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma

et al. 2018

View full text Add to dashboard Cite

Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC). The calcium-sensing receptor (CaSR) has been associated with bone metastasis in several different malignancies. We analyzed the impact of CaSR in bone metastasis in RCC in vitro and in vivo. The RCC cell line 786-O was stably transfected with the CaSR gene and treated with calcium alone or in combination with the CaSR antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent signaling molecules were analyzed. Calcium treated CaSR-transfected 768-O cells showed an increased adhesion to endothelial cells and the extracellular matrix components fibronectin and collagen I, but not to collagen IV. The chemotactic cell migration and proliferation was also induced by calcium. The activity of SHC, AKT, ERK, P90RSK and JNK were enhanced after calcium treatment of CaSR-transfected cells. These effects were abolished by NPS2143. Development of bone metastasis was evaluated in vivo in a mouse model. Intracardiac injection of CaSR-transfected 768-O cells showed an increased rate of bone metastasis. The results indicate CaSR as an important component in the mechanism of bone metastasis in RCC. Therefore, targeting CaSR might be beneficial in patients with bone metastatic RCC with a high CaSR expression.

show abstract

“…This is caused by diabetes mellitus, which is characterized by hyperglycemia due to a deficiency of insulin. Recently, it was shown that CaSR is one of the factors that modulates insulin secretion [52]. The constant hyperglycemic condition upregulates the expression of CaSR in cardiac fibroblasts which eventually leads to an increase in the intracellular calcium levels and activation of autophagy and the Smurf2 ubiquitin proteasome which is highly involved in protein degradation [52].…”

Section: Heart Failurementioning

confidence: 99%

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Sundararaman

Vorst

2021

IJMS

View full text Add to dashboard Cite

The calcium Sensing Receptor (CaSR) is a cell surface receptor belonging to the family of G-protein coupled receptors. CaSR is mainly expressed by parathyroid glands, kidneys, bone, skin, adipose tissue, the gut, the nervous system, and the cardiovascular system. The receptor, as its name implies is involved in sensing calcium fluctuations in the extracellular matrix of cells, thereby having a major impact on the mineral homeostasis in humans. Besides calcium ions, the receptor is also activated by other di- and tri-valent cations, polypeptides, polyamines, antibiotics, calcilytics and calcimimetics, which upon binding induce intracellular signaling pathways. Recent studies have demonstrated that CaSR influences a wide variety of cells and processes that are involved in inflammation, the cardiovascular system, such as vascular calcification, atherosclerosis, myocardial infarction, hypertension, and obesity. Therefore, in this review, the current understanding of the role that CaSR plays in inflammation and its consequences on the cardiovascular system will be highlighted.

show abstract

Activity of the calcium-sensing receptor influences blood glucose and insulin levels in rats

Abstract: We suggest that modulation of the CaR activity may participate in the mechanisms which mediate insulin secretion in rats.

Cited by 10 publications

References 23 publications

Diazoxide-induced hyperglycemia in rats is regulated by modulation of calcium receptor activity

Diazoxide-induced hyperglycemia in rats is regulated by modulation of calcium receptor activity

Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Contact Info

Product

Resources

About