ArticleCell metabolism2021
Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07335549 (Effect of Laparoscopic Sleeve Gastrectomy on Blood Isthmın Levels), which is not on this map. Cited by 72 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Laparoscopic Sleeve Gastrectomy on Blood Isthmın Levels: A Prospective Cohort Study
Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- New Mediators in the Crosstalk between Different Adipose Tissues.International journal of molecular sciences · 2024Pooled it
- Circulating isthmin-1 is associated with short-term metabolic changes after sleeve gastrectomy.Endocrine · 2026Article
- Maternal Serum Isthmin-1 as a Novel Biomarker for Late-Onset Fetal Growth Restriction.Journal of clinical medicine · 2026Article
- Serum Isthmin-1 in Gestational Diabetes Mellitus: A Case-Control Study Providing Preliminary Evidence of Elevated Levels and Association With Insulin Resistance.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- The Effects of Iloprost on Isthmin-1, Adropin and Trpc6 Immunoreactivity in an Experimental Lower Extremity Ischemia-Reperfusion Injury Model.Biomedicines · 2026Article
- Serum Isthmin-1 and Irisin profiles and their association with clinical parameters in fibromyalgia: a cross-sectional study.Rheumatology international · 2026Article
- Diagnostic and clinical associations of serum Isthmin-1 in acute ischemic stroke.Irish journal of medical science · 2026Article
- Circulating miR-326 and miR-532-3p: novel biomarkers for early gestational diabetes mellitus detection with high diagnostic accuracy.Journal of endocrinological investigation · 2026Article
- Non-syndromic premature ovarian insufficiency associated with monoallelic LIG4 mutation via haploinsufficiency.Journal of ovarian research · 2026Article
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- Loss of FoxO in skeletal muscle leads to disrupted muscle metabolism and exacerbates starvation-induced hepatic steatosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review).Molecular medicine reports · 2026Review
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- Evaluation of isthmin-1 immunoreactivity in gastric adenocarcinoma.Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery · 2026Article
- Metabolic characteristics and factors associated with prediabetes in Chinese adults based on real-world health examination data: a cross-sectional study.Frontiers in nutrition · 2026Article
- An Integrated Approach Combining Chemical Profiling, Network Pharmacology, and Experimental Validation Is Used to Clarify the Pharmacological Basis of the Yiqi-Tongluo-Huoxue-Mingmu Formula in Diabetic Retinopathy.Journal of diabetes research · 2026Article
- Podocalyxin, Isthmin-1, and Pentraxin-3 Immunoreactivities as Emerging Immunohistochemical Markers of Fibrosis in Chronic Hepatitis B.Biomedicines · 2025Article
- High serum isthmin-1 as a biomarker for the progression of renal function decline in patients with type 2 diabetes mellitus.BMC endocrine disorders · 2025Article
- Investigation of Isthmin-1 level in patients with polycystic ovary syndrome.BMC women's health · 2025Article
- Isthmin 1, matrix metalloproteinase 8 and asprosin as potential biomarkers in periodontitis with obesity.BMC oral health · 2025Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
20 authors at 5 institutions in 2 countries.
Zewen JiangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Meng ZhaoDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Laetitia VoilquinDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Yunshin JungDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mari A AikioDepartment of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Tanushi SahaiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA.
Florence Y DouDepartment of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Alexander M RocheDepartment of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Ivan Carcamo-OriveStanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joshua W KnowlesStanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Prevention Research Center, Stanford University, Stanford, CA 94305, USA.
Martin WabitschDivision of Pediatric Endocrinology and Diabetes, University Medical Center Ulm, Ulm, Germany.
Eric A AppelStanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics (Endocrinology), Stanford University, Stanford, CA 94305, USA.
Caitlin L MaikawaDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Joao Paulo CamporezDepartment of Physiology, Ribeirao Preto School of Medicine, University of Sao Paulo, Sao Paulo, Brazil; Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
Gerald I ShulmanDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA; Department of Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06519, USA.
Linus TsaiDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Evan D RosenDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Christopher D GardnerStanford University, Stanford, CA 94305, USA.
Bruce M SpiegelmanDepartment of Cell Biology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Katrin J SvenssonDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: katrinjs@stanford.edu.
Stanford University · USHarvard University · USBeth Israel Deaconess Medical Center · USYale University · USDana-Farber Cancer Institute · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MTranslational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4MYale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0MTransgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KAHN, BARBARA B. · 2000 to 2019
$31.4MYale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1MTransgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI CORKEY, BARBARA E. · 1992 to 2021
$25.0MStanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5MCONTROL OF ADIPOCYTE GENE EXPRESSION AND PHYSIOLOGYR37DK031405 · NIDDK · DANA-FARBER CANCER INSTITUTE · PI SPIEGELMAN, BRUCE M. · 1996 to 2013
$8.2MPGC1 proteins, meteorin-like and energy homeostasisR01DK061562 · NIDDK · DANA-FARBER CANCER INSTITUTE · PI SPIEGELMAN, BRUCE M. · 2002 to 2018
$7.2MTranscriptional Mechanisms of Human Insulin ResistanceR01DK102173 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ROSEN, EVAN D · 2015 to 2022
$4.4MMechanisms controlling fructose uptake and utilizationR01DK125260 · NIDDK · STANFORD UNIVERSITY · PI Katrin Jennifer Svensson · 2020 to 2026
$3.5MEpigenomics of Human Insulin ResistanceR01DK087092 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ROSEN, EVAN D · 2009 to 2013
$3.3MNCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA124435NIDDK NIH HHS K99 DK111916NIDDK NIH HHS P30 DK034989NIDDK NIH HHS P30 DK045735NIDDK NIH HHS P30 DK046200NIDDK NIH HHS P30 DK057521NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R00 DK111916NIDDK NIH HHS R01 DK031405NIDDK NIH HHS R01 DK061562NIDDK NIH HHS R01 DK087092NIDDK NIH HHS R01 DK102173NIDDK NIH HHS R01 DK116750NIDDK NIH HHS R01 DK119254NIDDK NIH HHS R01 DK120565NIDDK NIH HHS R01 DK125260NIDDK NIH HHS R37 DK031405
Abstract
With the increasing prevalence of type 2 diabetes and fatty liver disease, there is still an unmet need to better treat hyperglycemia and hyperlipidemia. Here, we identify isthmin-1 (Ism1) as an adipokine and one that has a dual role in increasing adipose glucose uptake while suppressing hepatic lipid synthesis. Ism1 ablation results in impaired glucose tolerance, reduced adipose glucose uptake, and reduced insulin sensitivity, demonstrating an endogenous function for Ism1 in glucose regulation. Mechanistically, Ism1 activates a PI3K-AKT signaling pathway independently of the insulin and insulin-like growth factor receptors. Notably, while the glucoregulatory function is shared with insulin, Ism1 counteracts lipid accumulation in the liver by switching hepatocytes from a lipogenic to a protein synthesis state. Furthermore, therapeutic dosing of recombinant Ism1 improves diabetes in diet-induced obese mice and ameliorates hepatic steatosis in a diet-induced fatty liver mouse model. These findings uncover an unexpected, bioactive protein hormone that might have simultaneous therapeutic potential for diabetes and fatty liver disease.
Indexed as
Diabetes Mellitus, Type 2Fatty LiverInsulin ResistanceAdipokinesAnimalsDiet, High-FatGlucoseIntercellular Signaling Peptides and ProteinsLipid MetabolismLipogenesisLiverMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesAdipokinesGlucoseIntercellular Signaling Peptides and Proteinsisthmin protein, mousePhosphatidylinositol 3-Kinasesadipokinecellular signalingdiabetesglucose uptakehepatic steatosislipogenesis
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT07335549ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.