Inositol, Glycogen, Insulin, and Six Nobelists

Larner, Joseph

doi:10.1074/jbc.x113.471177

Cited by 7 publications

(5 citation statements)

References 62 publications

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“…MI is an extensively studied metabolite [14][15][16][17] , whose isomers or derivatives participate in many fundamental physiological processes 18 . Among its nine possible stereo-isomers, MI is the most abundant 18 .…”

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confidence: 99%

The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

et al. 2020

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Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates—metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P2. MI and PI(4,5)P2 are precursors of PI(3,4,5)P3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI’s anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.

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confidence: 99%

The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

et al. 2020

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“…In a paper published last year, when he was 92 years old, chronicling his work and his life, 10 Larner wrote: "I am blessed to have had such superlative scientific mentors, a productive group of students and postdoctoral fellows, a loving wife of 65 years, three remarkable sons, and eight wonderful grandchildren. I am (still) working full time on insulin, which has entranced me for a long time.…”

Section: Obituariesmentioning

confidence: 99%

Joseph Larner

Stafford¹

2014

BMJ

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“…The cell-surface insulin receptor had been described, but virtually nothing was known about its intracellular signal transduction pathway. Insulin modulates the extent of phosphorylation of a number of important cytoplasmic enzymes and thus influences several important metabolic pathways (27). But would insulin, which plays such an important role in glucose, protein, and lipid metabolism, do all this without an effect on specific genes?…”

Section: Several Research Opportunities Are Exploredmentioning

confidence: 99%

In Pursuit of Genes of Glucose Metabolism

Granner

2015

Journal of Biological Chemistry

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Inositol, Glycogen, Insulin, and Six Nobelists

Cited by 7 publications

References 62 publications

The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

Joseph Larner

In Pursuit of Genes of Glucose Metabolism

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