Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver

Imai, Junta; Katagiri, Hideki; Yamada, Tetsuya; Ishigaki, Yasushi; Suzuki, Toshinobu; Kudo, Hirohito; Uno, Kenji; Hasegawa, Yutaka; Gao, Jinnan; Kaneko, Keizo; Ishihara, Hideharu; Niijima, Akira; Nakazato, Masamitsu; Asano, Tomohiko; Minokoshi, Yasuhiko; Oka, Yoshitomo

doi:10.1126/science.1163971

Cited by 212 publications

(197 citation statements)

References 26 publications

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“…13 In addition to these mechanisms, we have further unraveled that pancreatic β-cells are also regulated by in the nervemediated inter-organ communication system. 14 To elucidate the mechanisms underlying these compensatory responses of β-cells, we expressed several genes, known to be upregulated or activated in the livers of obesity models, in the livers of lean mice. Among them, we found that hepatic extracellular signal-regulated kinase (ERK), phosphorylation of which is reportedly enhanced in the liver of a murine obesity model, 15,16 plays an important role in compensatory β-cell responses.…”

Section: Identification Of a Novel Mechanism Regulating β-Cell Massmentioning

confidence: 99%

Identification of a novel mechanism regulating β-cell mass: Neuronal relay from the liver to pancreatic β-cells

Imai¹,

Oka²,

Katagiri³

2009

Islets

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Section: Identification Of a Novel Mechanism Regulating β-Cell Massmentioning

confidence: 99%

Identification of a novel mechanism regulating β-cell mass: Neuronal relay from the liver to pancreatic β-cells

Imai¹,

Oka²,

Katagiri³

2009

Islets

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“…They further showed that the pancreatic effects could be eliminated by ablation of afferent splanchnic nerve signalling, pancreatic vagotomy or bilateral midbrain transection, clearly demonstrating the involvement of a liver-brain-pancreas axis mediated by the nervous system. Although the splanchnic nerve does not exclusively innervate the liver, the transgene was not detected in any portion of the gastrointestinal tract in this experiment (80) . This demonstrated signalling pathway highlights the possibility that nutrient sensors expressed in hepatocytes, including AMP-dependent protein kinase (81,82) and mammalian target of rapamycin (83) , can respond to cellular energy status and communicate this status to the central nervous system.…”

Section: Weaknesses In the Modelmentioning

confidence: 95%

“…In a series of studies unrelated to peripheral regulation of feeding behaviour, Imai et al (80) clearly demonstrated that nerve signals originating from the liver reach the brain and subsequently impact other peripheral organs. In this work, adenoviral-mediated overexpression of extracellular-regulated kinase in liver parenchyma resulted in increased insulin secretion.…”

Section: Weaknesses In the Modelmentioning

confidence: 99%

“…In this work, adenoviral-mediated overexpression of extracellular-regulated kinase in liver parenchyma resulted in increased insulin secretion. Imai et al (80) first discovered that this response was driven by pancreatic b-cell proliferation, despite the lack of transgene expression in that organ. They further showed that the pancreatic effects could be eliminated by ablation of afferent splanchnic nerve signalling, pancreatic vagotomy or bilateral midbrain transection, clearly demonstrating the involvement of a liver-brain-pancreas axis mediated by the nervous system.…”

Section: Weaknesses In the Modelmentioning

confidence: 99%

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Control of food intake by metabolism of fuels: a comparison across species

Allen

Bradford

2012

Proc. Nutr. Soc.

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Research with laboratory species suggests that meals can be terminated by peripheral signals carried to brain feeding centres via hepatic vagal afferents, and that these signals are affected by oxidation of fuels. Pre-gastric fermentation in ruminants greatly alters fuels, allowing mechanisms conserved across species to be studied with different types and temporal absorption of fuels. These fuels include SCFA, glucose, lactate, amino acids and long-chain fatty acid (FA) isomers, all of which are absorbed and metabolised by different tissues at different rates. Propionate is produced by rumen microbes, absorbed within the timeframe of meals, and quickly cleared by the liver. Its hypophagic effects are variable, likely due to its fate; propionate is utilised for gluconeogenesis or oxidised and also stimulates oxidation of acetyl-CoA by anapleurosis. In contrast, acetate has little effect on food intake, likely because its uptake by the ruminant liver is negligible. Glucose is hypophagic in non-ruminants but not ruminants and unlike non-ruminant species, uptake of glucose by ruminant liver is negligible, consistent with the differences in hypophagic effects between them. Inhibition of FA oxidation increases food intake, whereas promotion of FA oxidation suppresses food intake. Hypophagic effects of fuel oxidation also vary with changes in metabolic state. The objective of this paper is to compare the type and utilisation of fuels and their effects on feeding across species. We believe that the hepatic oxidation theory allows insight into mechanisms controlling feeding behaviour that can be used to formulate diets to optimise energy balance in multiple species. Comparative metabolism: Food intake: Hepatic oxidationComparative metabolism can provide a valuable tool to improve understanding of physiological control mechanisms by investigating the similarities and differences across species. This paper addresses comparative aspects of the control of feeding behaviour by peripheral signals generated by oxidation of fuels. Research with rodents and other laboratory species indicates that inhibition of fuel oxidation stimulates feeding, whereas stimulation of oxidation inhibits feeding, and that the signal to brain feeding centres is via hepatic vagal afferents (1) . Feeding behaviour of rats has been related to energy charge in the liver and synergistic effects of metabolic inhibitors suggest an integrated mechanism with a common signal related to hepatic energy status from oxidation of various fuels (2) . However, the liver is only sparsely innervated with afferent fibres and the common hepatic vagus also innervates other tissues, including the duodenum (3) . The enterocyte was recently proposed as the primary sensor for fuel oxidation, casting doubt on a signal from the liver (4) . Evaluation of the ruminant model and comparison with non-ruminant models provides important insight into this issue because pre-gastric fermentation in ruminants greatly alters the type and temporal pattern of absorption of fuels. Rumen micr...

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“…In contrast to simple Mendelian disorders, complex disorders are not characterizable through a single gene defect but rather their etiology is a result of the interplay between several genes which may sometimes not even be in the same spatial domain [1].…”

Section: Introductionmentioning

confidence: 99%

Ethanol/alcohol pathways along with immune, cation and development may play a role in autism spectrum disorder

Saxena

2013

J Med Disord

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Introduction: Autism spectrum disorder or ASD was studied via copy number variations or CNVs and via windows straddling LoGS loci. We found strong concordance between our prior findings relating to development. Further, alcohol pathways were discovered. Methods: CNVs previously described in autism were studied and use of pathway overlaps in deducing mechanism is described. Results: CNVs related to autism were split into those falling within LoGS loci windows and those outside. Those inside related to immune function while those outside to alcohol pathways. Further, the enrichment of genes within windows centered on the loci showed mechanistic insights into autism. Discussion: Our analysis provides a mechanistic framework to define detailed mechanisms underlying autism. The found ethanol/ alcohol pathways rank topmost in the analysis conducted and provide another mechanistic insight into autism. Further the CNVs that contain such alcohol dehydrogenase or detoxifying genes show a loss in copy number as we would predict because alcohol has been known to affect the developing brain.

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Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver

Cited by 212 publications

References 26 publications

Identification of a novel mechanism regulating β-cell mass: Neuronal relay from the liver to pancreatic β-cells

Identification of a novel mechanism regulating β-cell mass: Neuronal relay from the liver to pancreatic β-cells

Control of food intake by metabolism of fuels: a comparison across species

Ethanol/alcohol pathways along with immune, cation and development may play a role in autism spectrum disorder

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