ORCID Profile
0000-0003-0811-6369
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Publisher: Wiley
Date: 14-02-2017
DOI: 10.1111/BPH.13711
Publisher: Elsevier BV
Date: 10-2015
Publisher: Frontiers Media SA
Date: 28-02-2020
Publisher: Bioscientifica
Date: 08-2014
DOI: 10.1530/JME-13-0200
Abstract: Glucagon-like peptide 1 receptor (GLP1R) agonists, such as exendin-4, potentiate glucose-stimulated insulin secretion and are currently used in the management of type 2 diabetes. Interestingly, GLP1R agonists also have the ability to augment β-cell mass. In this report, we provide evidence that in the presence of glucose, exendin-4 stimulates rodent islet cell DNA replication via the activation of ribosomal protein S6 kinase 1 (S6K1) and that this is mediated by the protein kinase B (PKB)-dependent activation of mTOR complex 1 (mTORC1). We show that activation of this pathway is caused by the autocrine or paracrine activation of the IGF1 receptor (IGF1R), as siRNA-mediated knockdown of the IGF1R effectively blocked exendin-4-stimulated PKB and mTORC1 activation. In contrast, pharmacological inactivation of the epidermal growth factor receptor has no discernible effect on exendin-4-stimulated PKB or mTORC1 activation. Therefore, we conclude that GLP1R agonists stimulate β-cell proliferation via the PKB-dependent stimulation of mTORC1/S6K1 whose activation is mediated through the autocrine aracrine activation of the IGF1R. This work provides a better understanding of the molecular basis of GLP1 agonist-induced β-cell proliferation which could potentially be exploited in the identification of novel drug targets that increase β-cell mass.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 21-10-2013
DOI: 10.1038/NUTD.2013.35
Abstract: The objective of this study was to determine whether ER stress correlates with β-cell dysfunction in obesity-associated diabetes. Quantitative RT-PCR and western blot analysis were used to investigate changes in the expression of markers of ER stress, the unfolded protein response (UPR) and β-cell function in islets isolated from (1) non-diabetic Zucker obese (ZO) and obese female Zucker diabetic fatty (fZDF) rats compared with their lean littermates and from (2) high-fat-diet-fed fZDF rats (HF-fZDF), to induce diabetes, compared with age-matched non-diabetic obese fZDF rats. Markers of an adaptive ER stress/UPR and β-cell function are elevated in islets isolated from ZO and fZDF rats compared with their lean littermates. In islets isolated from HF-fZDF rats, there was no significant change in the expression of markers of ER stress compared with age matched, obese, non-diabetic fZDF rats. These results provide evidence that obesity-induced activation of the UPR is an adaptive response for increasing the ER folding capacity to meet the increased demand for insulin. As ER stress is not exacerbated in high-fat-diet-induced diabetes, we suggest that failure of the islet to mount an effective adaptive UPR in response to an additional increase in insulin demand, rather than chronic ER stress, may ultimately lead to β-cell failure and hence diabetes.
Publisher: Oxford University Press (OUP)
Date: 05-2019
DOI: 10.1136/POSTGRADMEDJ-2019-136413
Abstract: South Western Sydney comprises of a culturally and linguistically erse (CALD) and lower socioeconomic status population group within the state of New South Wales. Geographic location and sociodemographic factors play important roles in access to healthcare and may be crucial in the success of time-critical acute stroke intervention. The aim of this study was to examine the trends in the delayed presentation to emergency department (ED) and identify factors associated with prehospital delay for an acute stroke/transient ischaemic attack (TIA) at a comprehensive stroke centre. Patient health-related data were extracted for stroke/TIA discharges for the period 2009–2017. Electronic medical record data were used to determine sociodemographic characteristics and prehospital factors, and their associations with delayed presentation≥4.5 hours from stroke onset were studied. During the 9-year period, population-adjusted stroke/TIA discharge rates increased from 540 to 676 per 100 000. A significant reduction in the proportion of patients presenting to ED& .5 hours (56% in 2009 versus 46% in 2017, p& .001) was observed. Younger patients aged 55–64 and 65–74 years, those belonging to Polynesia, South Asia and Mainland Southeast Asia, and those not using state ambulance as the mode of arrival to the hospital were at increased risk of prehospital delay. Comprehensive reappraisal of educational programmes for early stroke recognition is required in our region due to delayed ED presentations of younger and specific CALD communities of stroke/TIA patients.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2021
Publisher: Bioscientifica
Date: 04-2016
DOI: 10.1530/JME-15-0212
Abstract: The branched-chain amino acids (BCAA) leucine, isoleucine and valine, are essential amino acids that play a critical role in cellular signalling and metabolism. They acutely stimulate insulin secretion and activate the regulatory serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1), a kinase that promotes increased β-cell mass and function. The effects of BCAA on cellular function are dependent on their active transport into the mammalian cells via amino acid transporters and thus the expression and activity of these transporters likely influence β-cell signalling and function. In this report, we show that the System-L transporters are required for BCAA uptake into clonal β-cell lines and pancreatic islets, and that these are essential for signalling to mTORC1. Further investigation revealed that the System-L amino acid transporter 1 (LAT1) is abundantly expressed in the islets, and that knockdown of LAT1 using siRNA inhibits mTORC1 signalling, leucine-stimulated insulin secretion and islet cell proliferation. In summary, we show that the LAT1 is required for regulating β-cell signalling and function in islets and thus may be a novel pharmacological/nutritional target for the treatment and prevention of type 2 diabetes.
Publisher: Elsevier BV
Date: 06-2020
Location: China
No related grants have been discovered for Qi Cheng.