Pathophysiology of insulin resistance.
Insulin resistance is a feature of a number of clinical disorders, including type 2 diabetes/glucose intolerance, obesity, dyslipidaemia and hypertension clustering in the so-called metabolic syndrome. Insulin resistance in skeletal muscle manifests itself primarily as a reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport. Ectopic lipid accumulation plays an important role in inducing insulin resistance. Multiple defects in insulin signalling are responsible for impaired glucose metabolism in target tissues of subjects with features of insulin resistance. Inflammatory molecules and lipid metabolites inhibit insulin signalling by stimulating a number of different serine kinases which are responsible for serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1).
Sesti
Giorgio
G
Università Magna Graecia di Catanzaro, Campus Universitario Germaneto di Catanzaro, 88100 Catanzaro, Italy. sesti@unicz.it
D016207:Cytokines / Q000502:physiology; D005227:Fatty Acids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000502:physiology; D006003:Glycogen; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D009132:Muscles / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D011755:Pyrophosphatases / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013002:Somatomedins / Q000502:physiology; D000099221:Protein Kinase C zeta
D016207:Cytokines; D005227:Fatty Acids; D005947:Glucose; D051275:Glucose Transporter Type 4; D006003:Glycogen; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D010727:Phosphoric Diester Hydrolases; D011493:Protein Kinase C; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D051057:Proto-Oncogene Proteins c-akt; D011755:Pyrophosphatases; D011972:Receptor, Insulin; D013002:Somatomedins; D000099221:Protein Kinase C zeta; C516607:PTPN1 protein, human; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1