ArticleHuman molecular genetics2014
Defects in pancreatic development and glucose metabolism in SMN-depleted mice independent of canonical spinal muscular atrophy neuromuscular pathology.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier.British journal of clinical pharmacology · 2019Trial
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Ketosis-prone Diabetes as a Presentation of New-onset Diabetes in a Patient With Spinal Muscular Atrophy Type III.JCEM case reports · 2025Article
- Article
- Extracellular vesicles efficiently deliver survival motor neuron protein to cells in culture.Scientific reports · 2025Article
- Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy.Cell death & disease · 2023Article
- Mitochondrial Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2022Review
- Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.Skeletal muscle · 2022Article
- Nutritional, Gastrointestinal and Endo-Metabolic Challenges in the Management of Children with Spinal Muscular Atrophy Type 1.Nutrients · 2021Review
- Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy.JCI insight · 2021Article
- Metabolic Dysfunction in Spinal Muscular Atrophy.International journal of molecular sciences · 2021Review
- Revisiting the role of mitochondria in spinal muscular atrophy.Cellular and molecular life sciences : CMLS · 2021Review
- Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Review
- Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy.Scientific reports · 2020Article
- AAV9-Mediated Expression of SMN Restricted to Neurons Does Not Rescue the Spinal Muscular Atrophy Phenotype in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Abnormal fatty acid metabolism is a core component of spinal muscular atrophy.Annals of clinical and translational neurology · 2019Article
- Survival Motor Neuron (SMN) Protein Insufficiency Exacerbates Renal Ischemia/Reperfusion Injury.Frontiers in physiology · 2019Article
- Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With Mild Spinal Muscular Atrophy.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is characterized by motor neuron loss, caused by mutations or deletions in the ubiquitously expressed survival motor neuron 1 (SMN1) gene. We recently identified a novel role for Smn protein in glucose metabolism and pancreatic development in both an intermediate SMA mouse model (Smn(2B/-)) and type I SMA patients. In the present study, we sought to determine if the observed metabolic and pancreatic defects are SMA-dependent. We employed a line of heterozygous Smn-depleted mice (Smn(+/-)) that lack the hallmark SMA neuromuscular pathology and overt phenotype. At 1 month of age, pancreatic/metabolic function of Smn(+/-)mice is indistinguishable from wild type. However, when metabolically challenged with a high-fat diet, Smn(+/-)mice display abnormal localization of glucagon-producing α-cells within the pancreatic islets and increased hepatic insulin and glucagon sensitivity, through increased p-AKT and p-CREB, respectively. Further, aging results in weight gain, an increased number of insulin-producing β cells, hyperinsulinemia and increased hepatic glucagon sensitivity in Smn(+/-)mice. Our study uncovers and highlights an important function of Smn protein in pancreatic islet development and glucose metabolism, independent of canonical SMA pathology. These findings suggest that carriers of SMN1 mutations and/or deletions may be at an increased risk of developing pancreatic and glucose metabolism defects, as even small depletions in Smn protein may be a risk factor for diet- and age-dependent development of metabolic disorders.
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Registered trials
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