ArticlePloS one2019
Whole body glucoregulation and tissue-specific glucose uptake in a novel Akt substrate of 160 kDa knockout rat model.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Exofacial Epitope-Specific Antibodies Detect GLUT4 Translocation in Adult Human, Rat, and Mouse Skeletal Muscle.Diabetes · 2026Article
- Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise.Nature metabolism · 2024Article
- In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.Cardiovascular diabetology · 2024Article
- Phosphorylation of AS160-serine 704 is not essential for exercise-increase in insulin-stimulated glucose uptake by skeletal muscles from female or male rats.American journal of physiology. Endocrinology and metabolism · 2024Article
- Complex rearrangement in TBC1D4 in an individual with diabetes due to severe insulin resistance syndrome.European journal of human genetics : EJHG · 2024Article
- AS160 expression, but not AS160 Serine-588, Threonine-642, and Serine-704 phosphorylation, is essential for elevated insulin-stimulated glucose uptake by skeletal muscle from female rats after acute exercise.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Akt substrate of 160 kDa is essential for the calorie restriction-induced increase in insulin-stimulated glucose uptake by skeletal muscle of female rats.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2023Article
- Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion.Cardiovascular diabetology · 2023Article
- Illumination of the Endogenous Insulin-Regulated TBC1D4 Interactome in Human Skeletal Muscle.Diabetes · 2022Article
- NovelInternational journal of molecular sciences · 2022Article
- Article
- Exercise effects on γ3-AMPK activity, Akt substrate of 160 kDa phosphorylation, and glucose uptake in muscle of normal and insulin-resistant female rats.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance.Reviews in endocrine & metabolic disorders · 2021Review
- Zinc Supplementation and Strength Exercise in Rats with Type 2 Diabetes: Akt and PTP1B Phosphorylation in Nonalcoholic Fatty Liver.Biological trace element research · 2021Article
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- Glucose transporters in cardiovascular system in health and disease.Pflugers Archiv : European journal of physiology · 2020Review
- Excess Accumulation of Lipid Impairs Insulin Sensitivity in Skeletal Muscle.International journal of molecular sciences · 2020Review
- Principles of Genetic Engineering.Genes · 2020Review
- Exercise effects on γ3-AMPK activity, phosphorylation of Akt2 and AS160, and insulin-stimulated glucose uptake in insulin-resistant rat skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- In vivo glucoregulation and tissue-specific glucose uptake in female Akt substrate 160 kDa knockout rats.PloS one · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Akt substrate of 160 kDa (also called AS160 or TBC1D4) is a Rab GTPase activating protein and key regulator of insulin-stimulated glucose uptake which is expressed by multiple tissues, including skeletal muscle, white adipose tissue (WAT) and the heart. This study introduces a novel rat AS160-knockout (AS160-KO) model that was created using CRISPR/Cas9 technology. We compared male AS160-KO versus wildtype (WT) rats for numerous metabolism-related endpoints. Body mass, body composition, energy expenditure and physical activity did not differ between genotypes. Oral glucose intolerance was detected in AS160-KO versus WT rats (P<0.005). A hyperinsulinemic-euglycemic clamp (HEC) revealed insulin resistance for glucose infusion rate (P<0.05) with unaltered hepatic glucose production in AS160-KO versus WT rats. Genotype-effects on glucose uptake during the HEC: 1) was significantly lower in epitrochlearis (P<0.01) and extensor digitorum longus (P<0.05) of AS160-KO versus WT rats, and tended to be lower for AS160-KO versus WT rats in the soleus (P<0.06) and gastrocnemius (P<0.08); 2) tended to be greater for AS160-KO versus WT rats in white adipose tissue (P = 0.09); and 3) was significantly greater in the heart (P<0.005) of AS160-KO versus WT rats. GLUT4 protein abundance was significantly lower for AS160-KO versus WT rats in each tissue analyzed (P<0.01-0.001) except the gastrocnemius. Ex vivo insulin-stimulated glucose uptake was significantly lower (P<0.001) for AS160-KO versus WT rats in isolated epitrochlearis or soleus. Insulin-stimulated Akt phosphorylation (in vivo or ex vivo) did not differ between genotypes for any tissue tested. Ex vivo AICAR-stimulated glucose uptake by isolated epitrochlearis was significantly lower for AS160-KO versus WT rats (P<0.01) without genotype-induced alteration in AMP-activated protein phosphorylation. This unique AS160-KO rat model, which elucidated striking genotype-related modifications in glucoregulation, will enable future research aimed at understanding AS160's roles in numerous physiological processes in response to various interventions (e.g., diet and/or exercise).
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