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The IR1152 mutant insulin receptor selectively impairs insulin action in skeletal muscle but not in liver
- Source :
- Diabetes (N.Y.N.Y.) 49 (2000): 1194–1202., info:cnr-pdr/source/autori:Caruso M, Miele C, Oliva A, Condorelli G, Oriente F, Riccardi G, Capaldo B, Fiory F, Accili D, Formisano P, Beguinot F./titolo:The IR1152 mutant insulin receptor selectively impairs insulin action in skeletal muscle but not in liver./doi:/rivista:Diabetes (N.Y.N.Y.)/anno:2000/pagina_da:1194/pagina_a:1202/intervallo_pagine:1194–1202/volume:49, Scopus-Elsevier
- Publication Year :
- 2000
- Publisher :
- American Diabetes Association, 2000.
-
Abstract
- In patients harboring the IR1152 mutant insulin receptor, hepatic glucose production was normally suppressed by insulin. Hepatocytes without the insulin receptor gene and expressing IR1152 (Hep(MUT)) also showed normal insulin suppression of glucose production and full insulin response of glycogen synthase. In contrast, expression of the IR1152 mutant in skeletal muscle maximally increased glucose uptake and storage, preventing further insulin stimulation. IRS-1 phosphorylation was normally stimulated by insulin in both intact Hep(MUT) and L6 skeletal muscle cells expressing the IR1152 mutant (L6(MUT)). At variance, IRS-2 phosphorylation exhibited high basal levels with no further insulin-dependent increase in L6(MUT) but almost normal phosphorylation, both basal and insulin-stimulated, in the Hep(MUT) cells. In vitro, IR1152 mutant preparations from both the L6(MUT) and the Hep(MUT) cells exhibited increased basal and no insulin-stimulated phosphorylation of IRS-2 immobilized from either muscle or liver cells. IR1152 internalization in liver and muscle cells closely paralleled the ability of this mutant to phosphorylate IRS-2 in vivo in these cells. Block of receptor internalization (wild-type and mutant) in the liver and muscle cells also inhibited IRS-2, but not IRS-1, phosphorylation. Thus, the mechanisms controlling insulin receptor internalization differ in liver and skeletal muscle cells and may enable IR1152 to control glucose metabolism selectively in liver. In both cell types, receptor internalization seems necessary for IRS-2 but not IRS-1 phosphorylation.
- Subjects :
- Blood Glucose
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Insulin Receptor Substrate Proteins
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Glucose uptake
Mice
Internal medicine
Glucokinase
Internal Medicine
medicine
Animals
Insulin
Myocyte
Phosphorylation
Infusions, Intravenous
Muscle, Skeletal
Glycogen synthase
Mice, Knockout
biology
Intracellular Signaling Peptides and Proteins
Skeletal muscle
Phosphoproteins
Receptor, Insulin
Recombinant Proteins
Clone Cells
Insulin receptor internalization
Insulin receptor
Glucose
Glycogen Synthase
Endocrinology
medicine.anatomical_structure
Diabetes Mellitus, Type 2
Liver
biology.protein
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....70fe025d53d36186a9b29562e345025c