Abstract:
OBJECTIVE:GPR142 agonists are being pursued as novel diabetes therapies by virtue of their insulin secretagogue effects. But it is undetermined whether GPR142's functions in pancreatic islets are limited to regulating insulin secretion. The current study expands research on its action. METHODS AND RESULTS:We demonstrated by in situ hybridization and immunostaining that GPR142 is expressed not only in β cells but also in a subset of α cells. Stimulation of GPR142 by a selective agonist increased glucagon secretion in both human and mouse islets. More importantly, the GPR142 agonist also potentiated glucagon-like peptide-1 (GLP-1) production and its release from islets through a mechanism that involves upregulation of prohormone convertase 1/3 expression. Strikingly, stimulation of insulin secretion and increase in insulin content via GPR142 engagement requires intact GLP-1 receptor signaling. Furthermore, GPR142 agonist increased β cell proliferation and protected both mouse and human islets against stress-induced apoptosis. CONCLUSIONS:Collectively, we provide here evidence that local GLP-1 release from α cells defines GPR142's beneficial effects on improving β cell function and mass, and we propose that GPR142 agonism may have translatable and durable efficacy for the treatment of type 2 diabetes.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Lin HV,Wang J,Wang J,Li W,Wang X,Alston JT,Thomas MK,Briere DA,Syed SK,Efanov AMdoi
10.1016/j.molmet.2018.02.008subject
Has Abstractpub_date
2018-05-01 00:00:00pages
205-211issn
2212-8778pii
S2212-8778(18)30122-4journal_volume
11pub_type
杂志文章abstract:OBJECTIVE:During pregnancy, women normally increase their food intake and body fat mass, and exhibit insulin resistance. However, an increasing number of women are developing metabolic imbalances during pregnancy, including excessive gestational weight gain and gestational diabetes mellitus. Despite the negative health...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.12.005
更新日期:2014-12-19 00:00:00
abstract:OBJECTIVE:The glycoprotein hormone erythropoietin (EPO) is required for erythropoiesis, and the kidney is the primary site of adult EPO synthesis. Limited evidence has suggested that EPO could be detectable in the brain under certain conditions, but it remains unknown if the brain might have its own EPO system for biol...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.12.001
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.09.006
更新日期:2016-09-20 00:00:00
abstract:BACKGROUND:Evidence hints at the ability of β-cells to emerge from non-β-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous β-cell regeneration without genetic or pharmacological manipulations remain to be determined. METHODS & RESULTS:Using PANI...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.05.001
更新日期:2016-05-10 00:00:00
abstract:OBJECTIVE:Glucagon-like peptide 1 (GLP-1) enhances insulin secretion and protects β-cell mass. Diabetes therapies targeting the GLP-1 receptor (GLP-1R), expressed in numerous tissues, have diminished dose-response in patients with type 2 diabetes compared with healthy human controls. The aim of this study was to determ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.01.010
更新日期:2015-02-03 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.09.005
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:Despite the large body of work describing the tumor suppressor functions of Phosphatase and tensin homologue deleted on chromosome ten (PTEN), its roles in adipose homeostasis of adult animals are not yet fully understood. Here, we sought to determine the role of PTEN in whole-body adipose homeostasis. METHO...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.09.008
更新日期:2019-12-01 00:00:00
abstract:OBJECTIVE:Aging and weight gain lead to a decline in brown and beige adipocyte functionality that exacerbates obesity and insulin resistance. We sought to determine whether sphingolipids, such as ceramides, a class of lipid metabolites that accumulate in aging and overnutrition, are sufficient or necessary for the meta...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101145
更新日期:2020-12-19 00:00:00
abstract:OBJECTIVE:Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.10.001
更新日期:2014-10-16 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.01.019
更新日期:2018-04-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.10.014
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons. METHODS:MCH n...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.05.001
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:Functional investigation of novel gene/protein targets associated with adipocyte differentiation or function heavily relies on efficient and accessible tools to manipulate gene expression in adipocytes in vitro. Recent advances in gene-editing technologies such as CRISPR-Cas9 have not only eased gene editing ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.07.001
更新日期:2017-10-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101116
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate en...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.03.008
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:Dedifferentiation of pancreatic β-cells may reduce islet function in type 2 diabetes (T2D). However, the prevalence, plasticity and functional consequences of this cellular state remain unknown. METHODS:We employed single-cell RNAseq to detail the maturation program of α- and β-cells during human ontogeny. W...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101057
更新日期:2020-12-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.100979
更新日期:2020-06-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.11.007
更新日期:2019-02-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.06.002
更新日期:2015-06-15 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.03.016
更新日期:2017-06-21 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.07.011
更新日期:2016-08-08 00:00:00
abstract:OBJECTIVE:Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover, FFAs act via multip...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.02.001
更新日期:2016-02-13 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101052
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), play a paramount role in the central regulation of energy balance. Despite the substantial body of genetic evidence implicating BDNF- or TrkB-deficiency in human obesity, the critical brain region(s) contributing ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.08.002
更新日期:2015-08-18 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.10.015
更新日期:2018-01-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101120
更新日期:2021-01-01 00:00:00
abstract::11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specifi...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.04.008
更新日期:2014-05-02 00:00:00
abstract:OBJECTIVE:Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) an...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.12.005
更新日期:2018-02-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.06.013
更新日期:2016-06-30 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.03.001
更新日期:2015-03-10 00:00:00