Muscle and adipose tissue insulin resistance: malady without mechanism?
Autor: | David E. James, Samantha L. Hocking, James R. Krycer, Alison L Kearney, Daniel J. Fazakerley |
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Rok vydání: | 2019 |
Předmět: |
glucose transporter type 4
0301 basic medicine medicine.medical_specialty medicine.medical_treatment Adipose tissue Inflammation QD415-436 Type 2 diabetes 030204 cardiovascular system & hematology Mitochondrion Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Internal medicine medicine Hyperinsulinemia Animals Humans insulin signaling oxidants biology business.industry Muscles Insulin Thematic Review Series Biological Transport Cell Biology medicine.disease mitochondria Insulin receptor Glucose 030104 developmental biology Adipose Tissue biology.protein Insulin Resistance medicine.symptom business |
Zdroj: | Journal of Lipid Research, Vol 60, Iss 10, Pp 1720-1732 (2019) J Lipid Res |
ISSN: | 0022-2275 |
Popis: | Insulin resistance is a major risk factor for numerous diseases, including type 2 diabetes and cardiovascular disease. These disorders have dramatically increased in incidence with modern life, suggesting that excess nutrients and obesity are major causes of "common" insulin resistance. Despite considerable effort, the mechanisms that contribute to common insulin resistance are not resolved. There is universal agreement that extracellular perturbations, such as nutrient excess, hyperinsulinemia, glucocorticoids, or inflammation, trigger intracellular stress in key metabolic target tissues, such as muscle and adipose tissue, and this impairs the ability of insulin to initiate its normal metabolic actions in these cells. Here, we present evidence that the impairment in insulin action is independent of proximal elements of the insulin signaling pathway and is likely specific to the glucoregulatory branch of insulin signaling. We propose that many intracellular stress pathways act in concert to increase mitochondrial reactive oxygen species to trigger insulin resistance. We speculate that this may be a physiological pathway to conserve glucose during specific states, such as fasting, and that, in the presence of chronic nutrient excess, this pathway ultimately leads to disease. This review highlights key points in this pathway that require further research effort. |
Databáze: | OpenAIRE |
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