Regulation of Muscle Glucose Uptake In Vivo

Mandarino, Lawrence J.; Bonadonna, Riccardo C.; McGuinness, Owen P.; Halseth, Amy E.; Wasserman, David H.

doi:10.1002/cphy.cp070227

Cited by 10 publications

(5 citation statements)

References 312 publications

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“…An undisturbed glucose homeostasis and intact insulin secretary response and unperturbed sensitivity of the tissues to insulin are essential to maintain normal blood glucose levels [28–31]. …”

Section: Relation Between the Pathological Features Exhibited In Hmentioning

confidence: 99%

The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

Wang

2013

Journal of Diabetes Research

212

180

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Type 2 diabetes mellitus (T2DM) has an intersecting underlying pathology with thyroid dysfunction. The literature is punctuated with evidence indicating a contribution of abnormalities of thyroid hormones to type 2 DM. The most probable mechanism leading to T2DM in thyroid dysfunction could be attributed to perturbed genetic expression of a constellation of genes along with physiological aberrations leading to impaired glucose utilization and disposal in muscles, overproduction of hepatic glucose output, and enhanced absorption of splanchnic glucose. These factors contribute to insulin resistance. Insulin resistance is also associated with thyroid dysfunction. Hyper- and hypothyroidism have been associated with insulin resistance which has been reported to be the major cause of impaired glucose metabolism in T2DM. The state-of-art evidence suggests a pivotal role of insulin resistance in underlining the relation between T2DM and thyroid dysfunction. A plethora of preclinical, molecular, and clinical studies have evidenced an undeniable role of thyroid malfunctioning as a comorbid disorder of T2DM. It has been investigated that specifically designed thyroid hormone analogues can be looked upon as the potential therapeutic strategies to alleviate diabetes, obesity, and atherosclerosis. These molecules are in final stages of preclinical and clinical evaluation and may pave the way to unveil a distinct class of drugs to treat metabolic disorders.

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Section: Relation Between the Pathological Features Exhibited In Hmentioning

confidence: 99%

The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

Wang

2013

Journal of Diabetes Research

212

180

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“…This is because the complexities of the systems involved make it difficult to assess which characteristics translate into functional changes that regulate MGU. The most comprehensively studied of the systems involved in MGU is glucose transport 1–6 . Studies using a variety of techniques suggest that membrane transport plays an important role in control of basal MGU 7–15 .…”

Section: Muscle Glucose Uptake Is Controlled By Three Serial Stepsmentioning

confidence: 99%

Interaction of Physiological Mechanisms in Control of Muscle Glucose Uptake

Wasserman

Ayala

2005

Clin Exp Pharma Physio

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1. Control of glucose uptake is distributed between three steps. These are the rate that glucose is delivered to cells, the rate of transport into cells, and the rate that glucose is phosphorylated within these same cells. The functional limitations to each one of these individual steps has been difficult to assess because they are so closely coupled to each other. Studies have been performed in recent years using complex isotopic techniques or transgenic mouse models to shed new light on the role that each step plays in overall control of muscle glucose uptake. 2. Membrane glucose transport is a major barrier and glucose delivery and glucose phosphorylation are minor barriers to muscle glucose uptake in the fasted, sedentary state. GLUT-4 is translocated to the muscle membrane during exercise and insulin-stimulation. The result of this is that it can become so permeable to glucose that it is only a minor barrier to glucose uptake. 3. In addition to increasing glucose transport, exercise and insulin-stimulation also increase muscle blood flow and capillary recruitment. This effectively increases muscle glucose delivery and by doing so, works to enhance muscle glucose uptake. 4. There is a growing body of data that suggests that insulin resistance to muscle glucose uptake can be because of impairments in any one or more of the three steps that comprise the process.

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“…This occurs through an increase in the number of GLUT4 transporters at the cell membrane and enhanced disposal of glucose within the cell [59]. However, it is noteworthy that hyperglycemia, even in the absence of hyperinsulinemia, independently stimulates muscle glucose uptake [85]. To enhance the model’s ability for maintaining glucose homeostasis under different metabolic conditions, we assume that glucose uptake into the liver and skeletal muscle is stimulated by hyperglycemia, regardless of whether it is coupled with hyperinsulinemia or not.…”

Section: Blood Compartment and Dietary Intakementioning

confidence: 99%

Modelling sex-specific whole-body metabolic responses to feeding and fasting

Abo,

Layton

2024

Preprint

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Men exhibit a preference for carbohydrate metabolism, whereas women tend to favor lipid metabolism. Significant sex-based differences in energy oxidation are evident across various metabolic states, including fasting and feeding. While some of these differences can be attributed to variations in body composition such as increased fat mass in women and higher muscle mass in men, there are also inherent disparities in metabolic fluxes. For instance, women exhibit increased rates of lipolysis independent of body composition. However, there remain gaps in our understanding of how sex influences the metabolism of specific organs and how these differences manifest at the systemic level. To address some of these gaps, we developed a sex-specific, whole-body, multi-scale model of metabolism during feeding and fasting. Our model represents healthy young adults (male and female) and integrates cellular metabolism in organs with whole-body responses following various mixed meals, particularly high-carbohydrate and high-fat meals. We explored sex-related variations in metabolic responses during both the absorptive and postabsorptive phases following meals. Our model predicted that sex-related metabolic differences observed at the systemic level are driven by variations in nutrient storage and oxidation patterns in the liver, skeletal muscle, and adipose tissue. We hypothesized that sex differences in hepatic glucose output during short-term fasts are partly influenced by variations in free fatty acids, glycerol, and glycogen handling. We also identified a candidate mechanism, possibly more prevalent in the female liver, where lipids are redirected toward carbohydrate metabolism to support hepatic glucose production. Integrating sex-specific data and parameters into multi-scale frameworks holds promise for enhancing our understanding of human metabolism and its modulation by sex.

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Regulation of Muscle Glucose Uptake In Vivo

Abstract: The sections in this article are: Methodologies for Measurement of Skeletal Muscle Glucose Uptake Theories of Metabolic Control Kinetic Theory of Intact Organs Arteriovenous Differences Muscle Biopsies Positron Emission Tomography Nuclear Magnetic Resonance Spectro… Show more

Cited by 10 publications

References 312 publications

The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

Interaction of Physiological Mechanisms in Control of Muscle Glucose Uptake

Modelling sex-specific whole-body metabolic responses to feeding and fasting

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