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 PANIC-ATTAC mice, a model of titratable, acute β-cell apoptosis capable of autonomous, and effective islet mass regeneration, we demonstrate that an extended washout of residual tamoxifen activity is crucial for β-cell lineage tracing studies using the tamoxifen-inducible Cre/loxP systems. We further establish a doxycycline-inducible system to label different cell types in the mouse pancreas and pursued a highly quantitative assessment to trace adult β-cells after various metabolic challenges. Beyond proliferation of pre-existing β-cells, non-β-cells contribute significantly to the post-challenge regenerated β-cell pool. α-cell trans-differentiation is the predominant mechanism upon post-apoptosis regeneration and multiparity. No contributions from exocrine acinar cells were observed. During diet-induced obesity, about 25% of α-cells arise de novo from β-cells. Ectopic expression of Nkx6.1 promotes α-to-β conversion and insulin production. CONCLUSIONS:We identify the origins and fates of adult β-cells upon post-challenge upon autonomous regeneration of islet mass and establish the quantitative contributions of the different cell types using a lineage tracing system with high temporal resolution.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Ye R,Wang M,Wang QA,Spurgin SB,Wang ZV,Sun K,Scherer PEdoi
10.1016/j.molmet.2016.05.001subject
Has Abstractpub_date
2016-05-10 00:00:00pages
437-448issue
7issn
2212-8778pii
S2212-8778(16)30033-3journal_volume
5pub_type
杂志文章abstract：:Cytokine signaling has been connected to regulation of metabolism and energy balance. Numerous cytokine gene expression changes are stimulated by accumulation of bile acids in livers of young Foxa2 liver-conditional null mice. We hypothesized that bile acid-induced inflammation in young Foxa2 mutants, once chronic, af...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2013.08.005
更新日期：2013-08-24 00:00:00
abstract：OBJECTIVE:α/β-Hydrolase domain-6 (ABHD6) is a newly identified monoacylglycerol (MAG) lipase. We recently reported that it negatively regulates glucose stimulated insulin secretion (GSIS) in the β cells by hydrolyzing lipolysis-derived MAG that acts as a metabolic coupling factor and signaling molecule via exocytotic r...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.09.012
更新日期：2015-10-08 00:00:00
abstract：OBJECTIVE:Studies using the estrogen receptor alpha (ERα) knock-out (αERKO) mice have demonstrated that ERα plays a crucial role in various estrogen-mediated metabolic regulations. ERα is a ligand dependent transcription regulator and its activity is regulated by estrogenic compounds. ERα consists of two transcriptiona...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.09.006
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:Recent changes in nutrition and lifestyle have provoked an unprecedented increase in the prevalence of obesity and metabolic disorders. Recognition of the adverse effects on health has prompted intense efforts to understand the molecular determinants of insulin sensitivity and dysglycemia. In many respects, ...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2018.10.008
更新日期：2019-01-01 00:00:00
abstract：OBJECTIVE:A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work su...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.03.012
更新日期：2017-04-26 00:00:00
abstract：BACKGROUND:Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis,...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2016.05.016
更新日期：2016-06-06 00:00:00
abstract：BACKGROUND:Pancreatic β-cells adapt to high metabolic demand by expanding their β-cell mass and/or enhancing insulin secretion to maintain glucose homeostasis. Type 2 diabetes (T2D) is typically characterized by β-cell decompensation. SCOPE OF THE REVIEW:The current review focuses on summarizing the "omics" and "epi-o...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2019.06.003
更新日期：2019-09-01 00:00:00
abstract：BACKGROUND:In addition to their crucial role in reproduction, estrogens are key regulators of energy and glucose homeostasis and they also exert several cardiovascular protective effects. These beneficial actions are mainly mediated by estrogen receptor alpha (ERα), which is widely expressed in metabolic and vascular t...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2018.05.009
更新日期：2018-09-01 00:00:00
abstract：:The contribution of mitochondrial dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondrial dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondrial dysfunction fail to induce insulin resistance, suggesting...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.02.001
更新日期：2014-03-12 00:00:00
abstract：:Genetic variation in FFAR1 modulates insulin secretion dependent on non-esterified fatty acid (NEFA) concentrations. We previously demonstrated lower insulin secretion in minor allele carriers of PPARG Pro12Ala in high-NEFA environment, but the mode of action could not been revealed. We tested if this effect is mediat...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.07.001
更新日期：2014-07-07 00:00:00
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：BACKGROUND:Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistanc...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.101153
更新日期：2020-12-23 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:Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve...
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
abstract：:Decreased β-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore β-cell mass and normoglycemia is to improve β-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2012.08.006
更新日期：2012-08-17 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
更新日期：2020-02-01 00:00:00
abstract：OBJECTIVE:Pharmacological activation of adenosine signaling has been shown to increase β-cell proliferation and thereby β-cell regeneration in zebrafish and rodent models of diabetes. However, whether adenosine has an endogenous role in regulating β-cell proliferation is unknown. The objective of this study was to dete...
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：OBJECTIVES:Nutrient sensing by hypothalamic neurons is critical for the regulation of food intake and energy expenditure. We aimed to identify long- and medium-chain fatty acid species transported into the brain, their effects on energy balance, and the mechanisms by which they regulate activity of hypothalamic neurons...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.01.002
更新日期：2020-04-01 00:00:00
abstract：OBJECTIVES:The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101144
更新日期：2020-12-18 00:00:00
abstract：OBJECTIVE:Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.12.014
更新日期：2018-03-01 00:00:00
abstract：OBJECTIVE:Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatm...
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
abstract：OBJECTIVE:Adaptive thermogenesis, which is partly mediated by sympathetic input on brown adipose tissue (BAT), is a mechanism of heat production that confers protection against prolonged cold exposure. Various endogenous stimuli, for example, norepinephrine and FGF-21, can also promote the conversion of inguinal white ...
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
abstract：OBJECTIVES:Preferential damage to fast, glycolytic myofibers is common in many muscle-wasting diseases, including Duchenne muscular dystrophy (DMD). Promoting an oxidative phenotype could protect muscles from damage and ameliorate the dystrophic pathology with therapeutic relevance, but developing efficacious strategie...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101157
更新日期：2020-12-24 00:00:00
abstract：OBJECTIVE:Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signal...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.05.006
更新日期：2017-05-15 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
abstract：OBJECTIVE:Glucose promotes lipid remodelling in pancreatic β-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. METHODS:Using mass spectrometry (MS) we quantified changes in approximately 300...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.04.003
更新日期：2016-04-13 00:00:00
abstract：BACKGROUND:Sex differences in obesity and related diseases are well established. Gonadal hormones are a major determinant of these sex differences. However, sex differences in body size and composition are evident prior to exposure to gonadal hormones, providing evidence for gonadal-independent contributions attributab...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2018.04.003
更新日期：2018-09-01 00:00:00
abstract：BACKGROUND:Diabetes is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of preventive and therapeutic approaches. Genetic and environmental factors are the culprits involved in diabetes risk. Evidence from the last decade has highli...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.101041
更新日期：2020-11-01 00:00:00
abstract：OBJECTIVE:T cell activation triggers metabolic reprogramming to meet increased demands for energy and metabolites required for cellular proliferation. Ethanolamine phospholipid synthesis has emerged as a regulator of metabolic shifts in stem cells and cancer cells, which led us to investigate its potential role during ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2021.101170
更新日期：2021-01-20 00:00:00
