Marked depletion of GLUT4 glucose transporters in transverse tubules of skeletal muscle from streptozotocin‐induced diabetic rats

Dombrowski, Luce; Marette, André

doi:10.1016/0014-5793(95)01071-l

Cited by 15 publications

(17 citation statements)

References 39 publications

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“…3). GLUT4 is clearly the dominant insulin-responsive glucose transporter in muscle (14), and a decrease in GLUT4 expression as seen in this study (Table 2) would contribute to impaired muscle glucose uptake (15)(16)(17)(18)(19). The evidence of GLUT4 mRNA regulation in human diabetes is, however, not as conclusive (5, 20, 21).…”

Section: Resultsmentioning

confidence: 58%

Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice

Yechoor

Patti

Saccone

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

143

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Metabolic abnormalities underlying diabetes are primarily the result of the lack of adequate insulin action and the associated changes in protein phosphorylation and gene expression. To define the full set of alterations in gene expression in skeletal muscle caused by diabetes and the loss of insulin action, we have used Affymetrix oligonucleotide microarrays and streptozotocindiabetic mice. Of the genes studied, 235 were identified as changed in diabetes, with 129 genes up-regulated and 106 down-regulated. Analysis revealed a coordinated regulation at key steps in glucose and lipid metabolism, mitochondrial electron transport, transcriptional regulation, and protein trafficking. mRNAs for all of the enzymes of the fatty acid ␤-oxidation pathway were increased, whereas those for GLUT4, hexokinase II, the E1 component of the pyruvate dehydrogenase complex, and subunits of all four complexes of the mitochondrial electron transport chain were all coordinately down-regulated. Only about half of the alterations in gene expression in diabetic mice could be corrected toward normal after 3 days of insulin treatment and euglycemia. These data point to as of yet undefined mechanisms for highly coordinated regulation of gene expression by insulin and potential new targets for therapy of diabetes mellitus.

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Section: Resultsmentioning

confidence: 58%

Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice

Yechoor

Patti

Saccone

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

143

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“…Subcellular fractionation. Plasma membranes, transverse tubules (Ttubules), and GLUT4-enriched intracellular membranes were isolated from 8 -10 g of muscles (mixed gactrocnemius and quadriceps) using a procedure developed in our laboratory (4,22). This subcellular fractionation protocol has been extensively characterized with immunologic and enzymatic markers (4,22).…”

mentioning

confidence: 99%

Dietary Cod Protein Restores Insulin-Induced Activation of Phosphatidylinositol 3-Kinase/Akt and GLUT4 Translocation to the T-Tubules in Skeletal Muscle of High-Fat-Fed Obese Rats

et al. 2003

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Diet-induced obesity is known to cause peripheral insulin resistance in rodents. We have recently found that feeding cod protein to high-fat-fed rats prevents the development of insulin resistance in skeletal muscle. In the present study, we have further explored the cellular mechanisms behind this beneficial effect of cod protein on skeletal muscle insulin sensitivity. Rats were fed a standard chow diet or a high-fat diet in which the protein source was either casein, soy, or cod proteins for 4 weeks. Whole-body and muscle glucose disposal were reduced by ϳ50% in rats fed high-fat diets with casein or soy proteins, but these impairments were not observed in animals fed cod protein. Insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS) proteins were similar in muscle of chow-and high-fat-fed rats regardless of the dietary protein source. However, IRS-1-associated phosphatidylinositol (PI) 3-kinase activity was severely impaired (؊60%) in muscle of high-fatfed rats consuming casein or soy protein. In marked contrast, feeding rats with cod protein completely prevented the deleterious effect of fat feeding on insulinstimulated PI 3-kinase activity. The activation of the downstream kinase Akt/PKB by insulin, assessed by in vitro kinase assay and phosphorylation of GSK-3␤, were also impaired in muscle of high-fat-fed rats consuming casein or soy protein, but these defects were also fully prevented by dietary cod protein. However, no effect of cod protein was observed on atypical protein kinase C activity. Normalization of PI 3-kinase/Akt activation by insulin in rats fed high-fat diets with cod protein was associated with improved translocation of GLUT4 to the T-tubules but not to the plasma membrane. Taken together, these results show that dietary cod protein is a natural insulin-sensitizing agent that appears to prevent obesity-linked muscle insulin resistance by normalizing insulin activation of the PI 3-kinase/Akt pathway and by selectively improving GLUT4 translocation to the Ttubules. Diabetes 52:29 -37, 2003

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“…1A. However, the recovery of PM and TT and triad membranes is ~8 times greater than that of the L-IM fraction (5,21). Thus, even a small decrease in IR levels in these cell surface membrane fractions could explain the IR increments in the L-IM fraction of insulin-stimulated muscle.…”

Section: Insulin Receptor Internalization In Glut4 Vesiclesmentioning

confidence: 96%

“…Insulin (or saline) was injected in vivo for 4 or 30 min, and subcellular fractions enriched in either cell surface [PMs or TTs (TT and triad)] or GLUT4-enriched intracellular membranes (L-IM) were isolated as previously described (5,21). The endocytosis of IR was intense in the L-IM fraction as detected both by IR immunoblotting and insulin binding assays (Fig.…”

Section: Insulin Receptor Internalization In Glut4 Vesiclesmentioning

confidence: 99%

Sustained activation of insulin receptors internalized in GLUT4 vesicles of insulin-stimulated skeletal muscle.

2000

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Exposure of target cells to insulin results in the formation of ligand receptor complexes on the cell surface and their subsequent internalization into the endosomal apparatus. A current view is that endocytosis of the insulin receptor (IR) kinase results in its rapid deactivation and sorting of the IR back to the cell surface or to late endocytic compartments. We report herein that, in skeletal muscle, in vivo stimulation with insulin induced a rapid internalization of the IR to an insulinsensitive GLUT4-enriched intracellular membrane fraction. After 30 min of stimulation, IR content and tyrosine phosphorylation were increased by three and nine times in that fraction, respectively, compared with unstimulated muscles. In vitro autophosphorylation assays revealed that the kinase activity of internalized IRs was markedly augmented (eight to nine times) by insulin. In marked contrast with hepatic endosomes or adipocyte low-density microsomes, no IR tyrosine dephosphorylation activity was observed in GLUT4-enriched vesicles isolated from skeletal muscle. The activated IR was recovered in immunopurified GLUT4 vesicles after insulin stimulation. Insulin also increased tyrosine-phosphorylated insulin receptor substrate 1 and phosphatidylinositol 3-kinase adapter (p85) subunit contents in the intracellular membrane fraction, but these signaling molecules were not directly associated with GLUT4 vesicles. These results show that, in skeletal muscle, the activated IR reaches a GLUT4-enriched compartment where its activity is apparently sustained. We propose that compartmentalization of activated IRs to GLUT4 vesicles may play a role in sustaining insulin signaling at this locus in skeletal muscle.

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Marked depletion of GLUT4 glucose transporters in transverse tubules of skeletal muscle from streptozotocin‐induced diabetic rats

Cited by 15 publications

References 39 publications

Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice

Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice

Dietary Cod Protein Restores Insulin-Induced Activation of Phosphatidylinositol 3-Kinase/Akt and GLUT4 Translocation to the T-Tubules in Skeletal Muscle of High-Fat-Fed Obese Rats

Sustained activation of insulin receptors internalized in GLUT4 vesicles of insulin-stimulated skeletal muscle.

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