Neuroendocrine Control of Hepatic Gluconeogenesis

Glucose is intricately regulated in human body through a complex network of hormonal and neuronal factors. A series of evidence suggests that the gastrointestinal tract and the central nervous system play prominent roles in the regulation of glucose and energy homeostasis. The gut senses the nutrient supply to co-ordinate the release of hormones that activate neuronal networks in the brain, leading to the subsequent modulation of hepatic glucose output via the gut-brain-liver axis. The gut hormones also act on multiple peripheral tissues to regulate glucose level through an insulin-dependent and/or -independent mechanism. The brain, especially the hypothalamus, could also response to the hormones such as insulin and leptin and different nutrients to modulate the glucose homeostasis. In this chapter, we review the gut-brain-liver axis and the role of this organ interaction in the control of glucose homeostasis. A better understanding of these pathways will provide novel strategies for improved glycaemic control

Hormonal Regulation of Cholesterol Homeostasis

Cholesterol homeostasis is tightly regulated by a group of endocrine hormones under physiological conditions. Hormonal dysregulation is often associated with disturbed cholesterol homeostasis, resulting in many clinical disorders including atherosclerosis, fatty liver and metabolic syndrome. Circulating hormones regulate cholesterol metabolism by altering levels of relative genes either through their interactions with nuclear receptors or by interfering with bile acid signaling pathways. A better understanding of hormonal regulation of cholesterol metabolism would improve our likelihood of identifying effective and selective targets for the intervention of disturbed cholesterol. In this review, we discuss selected hormones critical for the cholesterol balance, including thyroid hormone, sex hormones, growth hormone, glucagon and irisin. We focus our discussion on the most recent advance in clinical epidemiology, animal mechanistic studies and the clinical application

Rspo1/Rspo3‐LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα‐SREBP2 pathway

R‐spondins (Rspos) are endogenous ligands of leucine‐rich repeat‐containing G‐protein‐coupled receptor 4 (LGR4). Rspos‐LGR4 signaling plays important roles in embryogenesis, gastrointestinal homeostasis, and food intake. Here, we investigated the impacts of Rspos‐LGR4 on hepatic cholesterol synthesis. Rspo1/3 and Lgr4 knockdown mice were used to investigate the impacts of Rspo1/3‐LGR4 on hepatic cholesterol synthesis. AMPKα agonist, antagonist, and shRNA were used to explore the downstream targets of Rspos‐LGR4 signaling. In our study, we reported that LGR4, Rspo1, and Rspo3 were highly expressed in hepatocytes and their expressions were sensitive to energy states. Rspo1 and Rspo3 reversed OA‐induced cholesterol synthesis, accompanying with increased the phosphorylation of AMPKα Thr172, reduced SREBP2 nuclear translocation, and Srebf2 mRNA expression. Conversely, hepatic LGR4 knockdown increased hepatic cholesterol synthesis and decreased the phosphorylation of AMPKα both in vitro and in vivo. Activation or inhibition of AMPKα significantly abolished the effects of LGR4 deficiency or Rspos, respectively, on cholesterol synthesis. Knockdown of AMPKα1 or/and AMPKα2 repressed Rspos‐induced inhibition on cholesterol synthesis. Our study indicates that Rspo1/Rspo3‐LGR4 signaling in hepatocytes suppresses cholesterol synthesis via the AMPKα‐SREBP2 pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163398/2/fsb221026.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163398/1/fsb221026_am.pd

Endothelin-Stimulated Capacitative Calcium Entry in Enteric Glial Cells: Synergistic Effects of Protein Kinase C Activity and Nitric Oxide

Depletion of intracellular calcium stores by agonist stimulation is coupled to calcium influx across the plasma membrane, a process termed capacitative calcium entry. Capacitative calcium entry was examined in cultured guinea pig enteric glial cells exposed to endothelin 3. Endothelin 3 (10 n M ) caused mobilization of intracellular calcium stores followed by influx of extracellular calcium. This capacitative calcium influx was inhibited by Ni 2+ (89 ± 2%) and by La 3+ (78 ± 2%) but was not affected by L-, N-, or P-type calcium channel blockers. Chelerythrine, a specific antagonist of protein kinase C, dose-dependently inhibited capacitative calcium entry. The nitric oxide synthase inhibitor N G -nitro-l-arginine decreased calcium influx in a dose-dependent manner. The combination of chelerythrine and N G -nitro-l-arginine produced synergistic inhibitory effects. Capacitative calcium entry occurs in enteric glial cells via lanthanum-inhibitable channels through a process regulated by protein kinase C and nitric oxide.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65161/1/j.1471-4159.1998.71010205.x.pd

Reducing Objectification Could Tackle Stigma in the COVID-19 Pandemic: Evidence from China

Stigmatization associated with the coronavirus disease 2019 (COVID-19) is expected to be a complex issue and to extend into the later phases of the pandemic, which impairs social cohesion and relevant individuals\u27 well-being. Identifying contributing factors and learning their roles in the stigmatization process may help tackle the problem. This study quantitatively assessed the severity of stigmatization against three different groups of people: people from major COVID-19 outbreak sites, those who had been quarantined, and healthcare workers; explored the factors associated with stigmatization within the frameworks of self-categorization theory and core social motives; and proposed solutions to resolve stigma. The cross-sectional online survey was carried out between April 21 and May 7, 2020, using a convenience sample, which yielded 1,388 valid responses. Employing data analysis methods like multivariate linear regression and moderation analysis, this study yields some main findings: (1) those from major COVID-19 outbreak sites received the highest level of stigma; (2) factors most closely associated with stigmatization, in descending order, are objectification and epidemic proximity in an autonomic aspect and fear of contracting COVID-19 in a controllable aspect; and (3) superordinate categorization is a buffering moderator in objectification-stigmatization relationship. These findings are important for further understanding COVID-19-related stigma, and they can be utilized to develop strategies to fight against relevant discrimination and bias. Specifically, reinforcing superordinate categorization by cultivating common in-group identity, such as volunteering and donating for containment of the pandemic, could reduce objectification and, thus, alleviate stigma

Inhibition of pancreatic protein secretion by ghrelin in the rat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65653/1/j.1469-7793.2001.0231k.x.pd

Photosynthetic and physiological responses of 9 camellia cultivars to high temperature stress and comprehensive evaluation of heat tolerance

Abstract [Objective] The heat tolerance of Camellia attracts more attention due to its rich flower types and colors and long flowering period. Suitable evaluation methods and indexes can provide bases for the heat-tolerance identification, the discovery of heat-tolerance germplasm, and the breeding of new cultivars of Camellia. [Methods] C. uraku and ‘Wirlinga Cascade’ were used as reference materials, and 7 new cultivars of cluster-flowering camellia were selected as test materials. They were cut in vase. After shortterm (5 h) or long-term (7 d) high-temperature (42 ℃/35 ℃) treatment, changes of morphological and photosynthetic indexes were investigated and heat tolerance was evaluated comprehensively. [Results] (1) The contents of chlorophyll, carotenoid, and chlorophyll a/b, net photosynthetic rate (Pn), and stomatal conductance (Gs) of ‘Chuizhi Fenyu’ and ‘Wirlinga Cascade’ were increased. Their maximum photochemical efficiency of PSⅡ (Fv/Fm ), potential activity of PSⅡ (Fv/Fo), and electron transport rate (ETR) were remained at a high level. Additionally, they did not show signs of heat damage after 7 days of high temperatures. Pn and Gs of ‘Jinye Fenyu’, ‘Shangzhi Huazhang’, and ‘Meigui Chun’ were decreased significantly under high temperature stress, while intercellular CO2 concentration (Ci) was increased. Among them, the Fv/Fm, Fv/Fo, and ETR of ‘Jinye Fenyu’ and ‘Shangzhi Huazhang’ were significantly reduced. After 7 days of long-term high temperature stress, these 3 cultivars showed severe heat damage or became dead. (2) 15 individual indicators were converted into 4 independent comprehensive indicators with cumulative contribution rate of 90% through principal component analysis. The comprehensive weight values of chlorophyll content, carotenoid content, and xanthophyll content were higher at 5 h under high temperature stress, and the comprehensive weight values of chlorophyll a/b, Fv/Fm, photochemical quenching coefficient (qP), and non-photochemical quenching coefficient (qN) were higher at 7 d under high temperature stress. [Conclusion] According to the comprehensive evaluation value D , ‘Chuizhi Fenyu’ is a heat-tolerance cultivar, ‘Shangzhi Yueguangqu’, ‘Shangzhi Huanlesong’, and ‘Sweet Gem’ are moderate tolerance, and ‘Meigui Chun’, ‘Shangzhi Huazhang’, and ‘Jinye Fenyu’ are the weakest among the new cultivars of cluster-flowering camellia. Chlorophyll, carotenoid, and xanthophyll contents can be used as the key indicators to analyze the short-term high temperature stress, while chlorophyll a/b, Fv/Fm, qP, and qN can be used as the key indicators to analyze the long-term high temperature stress of Camellia