Lewin Small

Lewin Small
University of Copenhagen · Novo Nordisk Foundation Center for Basic Metabolic Research

PhD

About

15
Publications
2,302
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243
Citations
Introduction
Lewin Small currently works in the Diabetes and Metabolism division at the Garvan Institute of Medical Research. Lewin does research in Biochemistry, Molecular Biology and Nutritional Biochemistry. Their most recent publication is 'Modelling insulin resistance in rodents by alterations in diet. What have "high fat" and high calorie diets revealed?.'

Publications

Publications (15)
Preprint
Obesity is generally associated with insulin resistance in liver and muscle and increased risk of developing type 2 diabetes, however there is a population of obese people that remain insulin sensitive. Similarly, recent work suggests that mice fed high carbohydrate diets can become obese without apparent glucose intolerance. To investigate this ph...
Article
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Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared g...
Article
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Objective The glucose tolerance test (GTT) is a widely used assay in preclinical research to interrogate glucose metabolism, but there is no standardised way by which glucose is administered. The aim of this study was to directly compare the effect of the route of glucose administration on glucose and insulin kinetics during a GTT in mice. Methods...
Article
Key points: Afadin is a ubiquitously expressed scaffold protein with a recently discovered role in insulin signaling and glucose metabolism. Insulin-stimulated phosphorylation of Afadin at S1795 occurs in insulin-responsive tissues such as adipose tissue, muscle, liver, pancreas and heart. Afadin abundance and AfadinS1795 phosphorylation are dynam...
Article
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In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery r...
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Key points: Exercising at different times of day elicits different effects on exercise performance and metabolic health however, the specific signals driving the observed time-of-day specific effects of exercise are not fully identified; Exercise influences the skeletal muscle circadian clock, but the relative contribution of muscle contraction an...
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Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority are located in non-coding DNA regions. This suggests t...
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Objective: Energy metabolism and insulin action follow a diurnal rhythm. It is therefore important that investigations into dysregulation of these pathways are relevant to the physiology of this diurnal rhythm. Methods: We examined glucose uptake, markers of insulin action, and the phosphorylation of insulin signaling intermediates in muscle of...
Article
One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collect...
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Skeletal muscle is a major tissue for glucose metabolism and can store glucose as glycogen, convert glucose to lactate via glycolysis and fully oxidise glucose to CO2. Muscle has a limited capacity for gluconeogenesis but can convert lactate and alanine to glycogen. Gluconeogenesis requires FBP2, a muscle specific form of fructose bisphosphatase th...
Article
Pyruvate dehydrogenase (PDH) activity is a key component of the glucose/fatty acid cycle hypothesis for the regulation of glucose uptake and metabolism. We have investigated whether acute activation of PDH in muscle can alleviate the insulin resistance caused by feeding animals a high fat diet. The importance of PDH activity in muscle glucose dispo...
Article
Grb10 is an adaptor-type signalling protein most highly expressed in tissues involved in insulin action and glucose metabolism, such as muscle, pancreas and adipose. Germline deletion of Grb10 in mice creates a phenotype with larger muscles and improved glucose homeostasis. However, it has not been determined whether Grb10 ablation specifically in...
Article
Grb10 is an intracellular adaptor protein which binds directly to several growth factor receptors, including those for insulin and insulin-like growth factor receptor-1 (IGF-1), and negatively regulates their actions. Grb10-ablated (Grb10-/-) mice exhibit improved whole body glucose homeostasis and an increase in muscle mass associated specifically...
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Full-text available
Dietary intake of long-chain fatty acids(LCFA) plays a causative role in insulin resistance and risk of diabetes. Whereas LCFA promote lipid accumulation and insulin resistance, diets rich in medium-chain fatty acids (MCFA) have been associated with increased oxidative metabolism and reduced adiposity, with little deleterious effects on insulin act...

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