Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction

Taneera, Jalal; Mohammed, Israa; Mohammed, Abdul Khader; Hachim, Mahmood Yaseen; Dhaiban, Sarah; Malek, Abdullah Imadeddin; Dunér, Pontus; Elemam, Noha Mousaad; Sulaiman, Nabil; Hamad, Mawieh; Salehi, Albert

doi:10.1016/j.mce.2019.110592

Cited by 15 publications

(22 citation statements)

References 29 publications

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“…While the ADMA17 expression pattern was similar in human β and α cells, it was mostly restricted to non-β-cells in mice islets [16]. This finding was not surprising as a degree of species specificity between humans and mice has been indicated [29].…”

Section: Discussionmentioning

confidence: 78%

Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors

Taneera

El‐Huneidi

Hamad

et al. 2020

Biology

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Cellular entry of SARS-CoV-2 is thought to occur through the binding of viral spike S1 protein to ACE2. The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. Our data show that pancreatic islets express all three receptors irrespective of diabetes status. The expression of ACE2 was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. The expression of the three receptors was statistically similar in young (≤40 years old) versus old (≥60 years old) donors. Obese (BMI > 30) donors have significantly higher expression levels of ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 correlated positively with BMI. The expression of the three receptors was statistically similar in muscle and subcutaneous adipose tissues obtained from diabetic and nondiabetic donors. Lastly, ACE2 expression was higher in sorted pancreatic β-cell relative to other endocrine cells. In conclusion, ACE2 expression is increased in diabetic human islets. More studies are required to investigate whether variations of ACE2 expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.

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Section: Discussionmentioning

confidence: 78%

Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors

Taneera

El‐Huneidi

Hamad

et al. 2020

Biology

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“…RPMI 1640 medium was used to culture and maintain INS-1 (832/13) cells (a gift from Dr. C. Newgard; Duke University, Durham, NC, USA) as described previously [ 35 , 36 ].…”

Section: Methodsmentioning

confidence: 99%

Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake

et al. 2022

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Carnosic acid (CA), a natural polyphenolic diterpene derived from Rosmarinus officinalis, has been proven to possess a broad spectrum of medicinal properties. Nevertheless, no studies on its impact on pancreatic β-cells have been conducted to date. Herein, clonal rat INS-1 (832/13) cells were pretreated with CA for 24 h and then incubated with streptozotocin (STZ) for 3 h. Several functional experiments were performed to determine the effect of CA on STZ-induced pancreatic β-cell damage, including cell viability assay, apoptosis analysis, and measurement of the level of insulin secretion, glucose uptake, malondialdehyde (MDA), reactive oxygen species (ROS), and proteins expression. STZ treatment decreased cell survival, insulin secretion, glucose uptake, and increased apoptosis, MDA, and ROS production in INS-1 cells. Furthermore, protein expression/phosphorylation analysis showed significant down-regulation in insulin, PDX-1, PI3K, AKT/p-AKT, and Bcl2. On the other hand, expression of BAX and BAD and cleaved PARP were significantly increased. Interestingly, preincubation with CA reversed the adverse impact of STZ at the cellular and protein expression levels. In conclusion, the data indicate that CA protects β-cells against STZ-induced damage, presumably through its modulatory effect on the different pathways, including the Pi3K/AKT/PDX-1/insulin pathway and mitochondria-mediated apoptosis.

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“…The clonal rat INS-1 (832/13) cells (a gift from Dr. C. Newgard; Duke University, North Carolina, USA) were maintained in a complete RPMI 1640 medium as previously described [ 33 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

The Coffee Diterpene, Kahweol, Ameliorates Pancreatic β-Cell Function in Streptozotocin (STZ)-Treated Rat INS-1 Cells through NF-kB and p-AKT/Bcl-2 Pathways

et al. 2021

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Kahweol is a diterpene molecule found in coffee that exhibits a wide range of biological activity, including anti-inflammatory and anticancer properties. However, the impact of kahweol on pancreatic β-cells is not known. Herein, by using clonal rat INS-1 (832/13) cells, we performed several functional experiments including; cell viability, apoptosis analysis, insulin secretion and glucose uptake measurements, reactive oxygen species (ROS) production, as well as western blotting analysis to investigate the potential role of kahweol pre-treatment on damage induced by streptozotocin (STZ) treatment. INS-1 cells pre-incubated with different concentrations of kahweol (2.5 and 5 µM) for 24 h, then exposed to STZ (3 mmol/L) for 3 h reversed the STZ-induced effect on cell viability, apoptosis, insulin content, and secretion in addition to glucose uptake and ROS production. Furthermore, Western blot analysis showed that kahweol downregulated STZ-induced nuclear factor kappa B (NF-κB), and the antioxidant proteins, Heme Oxygenase-1 (HMOX-1), and Inhibitor of DNA binding and cell differentiation (Id) proteins (ID1, ID3) while upregulated protein expression of insulin (INS), p-AKT and B-cell lymphoma 2 (BCL-2). In conclusion, our study suggested that kahweol has anti-diabetic properties on pancreatic β-cells by suppressing STZ induced apoptosis, increasing insulin secretion and glucose uptake. Targeting NF-κB, p-AKT, and BCL-2 in addition to antioxidant proteins ID1, ID3, and HMOX-1 are possible implicated mechanisms.

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Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction

Cited by 15 publications

References 29 publications

Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors

Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors

Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake

The Coffee Diterpene, Kahweol, Ameliorates Pancreatic β-Cell Function in Streptozotocin (STZ)-Treated Rat INS-1 Cells through NF-kB and p-AKT/Bcl-2 Pathways

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