22 results on '"Pessin, Jeffrey E."'
Search Results
2. High basal cell surface levels of fish GLUT4 are related to reduced sensitivity of insulin-induced translocation toward GGA and AS 160 inhibition in adipocytes
- Author
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Capilla, Encarnacion, Diaz, Monica, Hou, June Chunqiu, Planas, Josep V., and Pessin, Jeffrey E.
- Subjects
Fat cells -- Physiological aspects ,Fat cells -- Research ,Blood sugar -- Physiological aspects ,Blood sugar -- Research ,Insulin -- Health aspects ,Insulin -- Research ,Carrier proteins -- Physiological aspects ,Carrier proteins -- Research ,Biological sciences - Abstract
Glucose entry into cells is mediated by a family of facilitative transporter proteins (GLUTs). In mammals, GLUT4 is expressed in insulin-sensitive tissues and is responsible for the postprandial uptake of glucose. In fish, GLUT4 also mediates insulin-regulated glucose entry into cells but differs from mammalian GLUT4 in its affinity for glucose and in protein motifs known to be important for the traffic of GLUT4. In this study, we have characterized the intracellular and plasma membrane (PM) traffic of two orthologs of GLUT4 in fish, trout (btGLUT4) and salmon (okGLUT4), that do not share the amino terminal FQQI targeting motif of mammalian GLUT4. btGLUT4 (FQHL) and, to a lesser extent, okGLUT4 (FQQL) showed higher basal PM levels, faster traffic to the PM after biosynthesis, and earlier acquisition of insulin responsiveness than rat GLUT4. Furthermore, btGLUT4 showed a similar profile of internalization than rat GLUT4. Expression of the dominant-interfering AS160-4P mutant caused a significant decrease in the insulin-induced PM levels of okGLUT4 and rat GLUT4 and, to a lesser extent, of btGLUT4, suggesting that btGLUT4 has reduced retention into the IRC. Contrary to rat GLUT4 and okGLUT4, the presence of btGLUT4 at the PM under insulinstimulated conditions was not affected by coexpression of a dominant-interfering GGA mutant. These data suggest that fish GLUT4 follow a different trafficking pathway to the PM compared with rat GLUT4 that seems to be relatively independent of GGA. These results indicate that the regulated trafficking characteristics of GLUT4 have been modified during evolution from fish to mammals. Golgi-localized [gamma]-ear-containing Arf-binding protein; trout; salmon; glucose transport; glucose transporter 4; 3T3-L1 cells doi: 10.1152/ajpendo.00547.2009
- Published
- 2010
3. Adipocytes support cAMP-dependent translocation of aquaporin-2 from intracellular sites distinct from the insulin-responsive GLUT4 storage compartment
- Author
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Procino, Giuseppe, Caces, Donne Donne, Valenti, Giovanna, and Pessin, Jeffrey E.
- Subjects
Exocytosis -- Research ,Fat cells -- Research ,Biological sciences - Abstract
Aquaporin-2 (AQP2), when expressed in fully differentiated 3T3-L1 adipocytes, displays cAMP-dependent plasma membrane translocation in a manner similar to its behavior in renal epithelial cells. The translocation of AQP2 required phosphorylation at serine 256, as the expression of AQP2/S256D was constitutively plasma membrane localized, whereas AQP2/S256A was refractory to forskolin stimulation. Unlike GLUT4, this property is not inhibited by depolymerization of cortical actin. In addition, coexpression with the dominant negative form of TC10 (TC10/T31N) or inhibition of phosphatidylinositol 3-kinase did not abrogate the cAMP-mediated response. Under basal conditions, AQP2 is localized in both the perinuclear region and in punctate vesicles scattered within the periphery of the cell. Two- and three-dimensional confocal immunofluorescence microscopy demonstrated that the adipocyte AQP2 cAMP-responsive compartment was distinct from the GLUT4 insulin-responsive compartment. Consistent with this conclusion, insulin was an effective stimulator of GLUT4 translocation but had no effect on AQP2. Conversely, forskolin induced AQP2 translocation but not GLUT4. Colocalization studies with the early endosomal marker EEA1 and transferrin receptor suggested that the AQP2 compartment is mostly distinct from endosomal vesicles. Interestingly. however, the peripheral AQP2 vesicles significantly overlapped vesicle-associated membrane protein-2, underscoring the role of the latter in hormone-regulated exocytosis. To acquire insulin responsiveness following biosynthesis, GLUT4 undergoes a slow sorting step that requires 6-9 h. In contrast, AQP2 rapidly acquires forskolin responsiveness (3 h following biosynthesis) and directly enters the cAMP-regulated compartment without transiting the plasma membrane. Together, these data demonstrate that adipocytes display two different intracellular sorting mechanisms that direct distinct hormone-sensitive partitioning of GLUT4 and AQP2. hormone-regulated exocytosis; trans-Golgi network: renal epithelial cells
- Published
- 2006
4. Initial entry of IRAP into the insulin-responsive storage compartment occurs prior to basal or insulin-stimulated plasma membrane recycling
- Author
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Liu, Gang, Hou, June Chunqiu, Watson, Robert T., and Pessin, Jeffrey E.
- Subjects
Biosynthesis -- Research ,Cell membranes -- Research ,Insulin resistance -- Research ,Biological sciences - Abstract
To examine the acquisition of insulin sensitivity after the initial biosynthesis of the insulin-responsive aminopeptidase (IRAP), 3T3-L1 adipocytes were transfected with an enhanced green fluorescent protein-IRAP (EGFP-IRAP) fusion protein. In the absence of insulin, IRAP was rapidly localized (1-3 h) to secretory membranes and retained in these intracellular membrane compartments with little accumulation at the plasma membrane. However, insulin was unable to induce translocation to the plasma membrane until 6-9 h after biosynthesis. This was in marked contrast to another type II membrane protein (syntaxin 3) that rapidly defaulted to the plasma membrane 3 h after expression. In parallel with the time-dependent acquisition of insulin responsiveness, the newly synthesized IRAP protein converted from a brefeldin A-sensitive to a brefeldin A-insensitive state. The initial trafficking of IRAP to the insulin-responsive compartment was independent of plasma membrane endocytosis, as expression of a dominant-interfering dynamin mutant (DyrdK44A) inhibited transferrin receptor endocytosis but had no effect on the insulin-stimulated translocation of the newly synthesized IRAP protein. insulin-responsive aminopeptidase; trafficking; insulin; cargo selection; biosynthesis
- Published
- 2005
5. Functional characterization of an insulin-responsive glucose transporter (GLUT4) from fish adipose tissue
- Author
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Capilla, Encarnacion, Diaz, Monica, Albalat, Amaya, Navarro, Isabel, Pessin, Jeffrey E., Keller, Konrad, and Planas, Josep V.
- Subjects
Oocytes -- Research ,Insulin -- Research ,Biological sciences - Abstract
Glucose transport across the plasma membrane is mediated by a family of glucose transporter proteins (GLUTs), several of which have been identified in mammalian, avian, and, more recently, in fish species. Here, we report on the cloning of a salmon GLUT from adipose tissue with a high sequence homology to mammalian GLUT4 that has been named okGLUT4. Kinetic analysis of glucose transport following expression in Xenopus laevis oocytes demonstrated a 7.6 [+ or -] 1.4 mM [K.sub.m] for 2-deoxyglucose (2-DG) transport measured under zero-trans conditions and 14.4 [+ or -] 1.5 mM by equilibrium exchange of 3-O-methylglucose. Transport of 2-DG by okGLUT4-injected oocytes was stereospecific and was competed by D-glucose, D-mannose, and, to a lesser extent, D-galactose and D-fructose. In addition, 2-DG uptake was inhibited by cytochalasin B and ethylidene glucose. Moreover, insulin stimulated glucose uptake in Xenopus oocytes expressing okGLUT4 and in isolated trout adipocytes, which contain the native form of okGLUT4. Despite differences in protein motifs important for insulin-stimulated translocation of mammalian GLUT4, okGLUT4 was able to translocate to the plasma membrane from intracellular localization sites in response to insulin when expressed in 3T3-LI adipocytes. These data demonstrate that okGLUT4 is a structural and functional fish homolog of mammalian GLUT4 but with a lower affinity for glucose, which could in part explain the lower ability of fish to clear a glucose load. glucose uptake; Xenopus oocytes; immunolocalization
- Published
- 2004
6. Comparative impact of dietary carbohydrates on the liver transcriptome in two strains of mice.
- Author
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Yuling Chi, Dou Yeon Youn, Xiaoli, Alus M., Li Liu, Yunping Qiu, Kurland, Irwin J., Pessin, Jacob B., Fajun Yang, and Pessin, Jeffrey E.
- Subjects
DIETARY carbohydrates ,TRANSCRIPTOMES ,GENE expression ,FRUCTOSE ,CELLULAR signal transduction ,LABORATORY mice - Abstract
Excessive long-term consumption of dietary carbohydrates, including glucose, sucrose, or fructose, has been shown to have significant impact on genome-wide gene expression, which likely results from changes in metabolic substrate flux. However, there has been no comprehensive study on the acute effects of individual sugars on the genome-wide gene expression that may reveal the genetic changes altering signaling pathways, subsequent metabolic processes, and ultimately physiological/pathological responses. Considering that gene expressions in response to acute carbohydrate ingestion might be different in nutrient sensitive and insensitive mammals, we conducted comparative studies of genome-wide gene expression by deep mRNA sequencing of the liver in nutrient sensitive C57BL/6J and nutrient insensitive BALB/cJ mice. Furthermore, to determine the temporal responses, we compared livers from mice in the fasted state and following ingestion of standard laboratory mouse chow supplemented with plain drinking water or water containing 20% glucose, sucrose, or fructose. Supplementation with these carbohydrates induced unique extents and temporal changes in gene expressions in a strain specific manner. Fructose and sucrose stimulated gene changes peaked at 3 h postprandial, whereas glucose effects peaked at 12 h and 6 h postprandial in C57BL/6J and BABL/cJ mice, respectively. Network analyses revealed that fructose changed genes were primarily involved in lipid metabolism and were more complex in C57BL/6J than in BALB/cJ mice. These data demonstrate that there are qualitative and antitative differences in the normal physiological responses of the liver between these two strains of mice and C57BL/6J is more sensitive to sugar intake than BALB/cJ. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
7. Skeletal muscle fibrosis is associated with decreased muscle inflammation and weakness in patients with chronic kidney disease
- Author
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Abramowitz, Matthew K., primary, Paredes, William, additional, Zhang, Kehao, additional, Brightwell, Camille R., additional, Newsom, Julia N., additional, Kwon, Hyok-Joon, additional, Custodio, Matthew, additional, Buttar, Rupinder S., additional, Farooq, Hina, additional, Zaidi, Bushra, additional, Pai, Rima, additional, Pessin, Jeffrey E., additional, Hawkins, Meredith, additional, and Fry, Christopher S., additional
- Published
- 2018
- Full Text
- View/download PDF
8. Skeletal muscle fibrosis is associated with decreased muscle inflammation and weakness in patients with chronic kidney disease.
- Author
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Abramowitz, Matthew K., Paredes, William, Kehao Zhang, Brightwell, Camille R., Newsom, Julia N., Hyok-Joon Kwon, Custodio, Matthew, Buttar, Rupinder S., Farooq, Hina, Zaidi, Bushra, Pai, Rima, Pessin, Jeffrey E., Hawkins, Meredith, and Fry, Christopher S.
- Abstract
Muscle dysfunction is an important cause of morbidity among patients with chronic kidney disease (CKD). Although muscle fibrosis is present in a CKD rodent model, its existence in humans and its impact on physical function are currently unknown. We examined isometric leg extension strength and measures of skeletal muscle fibrosis and inflammation in vastus lateralis muscle from CKD patients (n = 10) and healthy, sedentary controls (n = 10). Histochemistry and immunohistochemistry were used to assess muscle collagen and macrophage and fibro/adipogenic progenitor (FAP) cell populations, and RT-qPCR was used to assess muscle-specific inflammatory marker expression. Muscle collagen content was significantly greater in CKD compared with control (18.8 ± 2.1 vs. 11.7 ± 0.7% collagen area, P = 0.008), as was staining for collagen I, pro-collagen I, and a novel collagen-hybridizing peptide that binds remodeling collagen. Muscle collagen was inversely associated with leg extension strength in CKD (r = −0.74, P = 0.01). FAP abundance was increased in CKD, was highly correlated with muscle collagen (r = 0.84, P < 0.001), and was inversely associated with TNF-α expression (r = −0.65, P = 0.003). TNF-α, CD68, CCL2, and CCL5 mRNA were significantly lower in CKD than control, despite higher serum TNF-α and IL-6. Immunohistochemistry confirmed fewer CD68+ and CD11b+ macrophages in CKD muscle. In conclusion, skeletal muscle collagen content is increased in humans with CKD and is associated with functional parameters. Muscle fibrosis correlated with increased FAP abundance, which may be due to insufficient macrophage-mediated TNF-α secretion. These data provide a foundation for future research elucidating the mechanisms responsible for this newly identified human muscle pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
9. Transmembrane domain length determines intracellular membrane compartment localization of syntaxins 3, 4, and 5
- Author
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WATSON, ROBERT T. and PESSIN, JEFFREY E.
- Subjects
Cell membranes -- Physiological aspects ,Cells -- Permeability ,Biological sciences - Abstract
Transmembrane domain length determines intracellular membrane compartment localization of syntaxins 3, 4, and 5. Am J Physiol Cell Physiol 281: C215-C223, 2001.--Insulin recruits glucose transporter 4 (GLUT-4) vesicles from intracellular stores to the plasma membrane in muscle and adipose tissue by specific interactions between the vesicle membrane-soluble N-ethylmaleimide-sensitive factor attachment protein target receptor (SNARE) protein VAMP-2 and the target membrane SNARE protein syntaxin 4. Although GLUT-4 vesicle trafficking has been intensely studied, few have focused on the mechanism by which the SNAREs themselves localize to specific membrane compartments. We therefore set out to identify the molecular determinants for localizing several syntaxin isoforms, including syntaxins 3, 4, and 5, to their respective intracellular compartments (plasma membrane for syntaxins 3 and 4; cis-Golgi for syntaxin 5). Analysis of a series of deletion and chimeric syntaxin constructs revealed that the 17-amino acid transmembrane domain of syntaxin 5 was sufficient to direct the cis-Golgi localization of several heterologous reporter constructs. In contrast, the longer 25-amino acid transmembrane domain of syntaxin 3 was sufficient to localize reporter constructs to the plasma membrane. Furthermore, truncation of the syntaxin 3 transmembrane domain to 17 amino acids resulted in a complete conversion to cis-Golgi compartmentalization that was indistinguishable from syntaxin 5. These data support a model wherein short transmembrane domains ([is less than or equal to] 17 amino acids) direct the cis-Golgi localization of syntaxins, whereas long transmembrane domains ([is greater than or equal to] 23 amino acids) direct plasma membrane localization. syntaxin; localization; membrane targeting
- Published
- 2001
10. Functional comparison of the role of dynamin 2 splice variants on GLUT-4 endocytosis in 3T3L1 adipocytes
- Author
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KAO, AIMEE W., YANG, CHUNMEI, and PESSIN, JEFFREY E.
- Subjects
Insulin -- Physiological aspects ,Endocytosis -- Physiological aspects ,Biological sciences - Abstract
Functional comparison of the role of dynamin 2 splice variants on GLUT-4 endocytosis in 3T3L1 adipocytes. Am J Physiol Endocrinol Metab 278: E825-E831, 2000.--Previously, we reported that expression of a dominant-interfering neuronal-specific dynamin 1 (K44A/dynamin 1) inhibited the plasma membrane internalization of GLUT-4 in 3T3L1 adipocytes (15). To investigate the rote of the ubiquitously expressed isoform of dynamin, dynamin 2, on adipocyte GLUT-4 internalization, and to determine whether dynamin splice variants have functional specificity, we expressed each of the four dynamin 2 isoforms (aa, ab, ba, and bb) as either wild-type proteins or GTPase-defective mutants. When expressed as enhanced green fluorescent protein (EGFP) fusions, these isoforms were found to have overlapping subcellular distributions being localized throughout the cell cytoplasm, on punctate vesicles and in a perinuclear compartment. This distribution was qualitatively similar to that of endogenous dynamin 2 and overlapped with GLUT-4 in the basal state. Expression of wild-type dynamin 2 isoforms had no effect on the basal or insulin-stimulated distribution of GLUT-4; however, expression of the dominant-interfering dynamin 2 mutants inhibited GLUT-4 endocytosis. These data demonstrate that dynamin 2 is required for GLUT-4 endocytosis in 3T3L1 adipocytes and suggest that, relative to GLUT-4 trafficking, the dynamin 2 splice variants have overlapping functions and are probably not responsible for mediating distinct GLUT-4 budding events. insulin; translocation
- Published
- 2000
11. Suppression of mTORC1 activation in acid-α-glucosidase-deficient cells and mice is ameliorated by leucine supplementation
- Author
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Shemesh, Adi, primary, Wang, Yichen, additional, Yang, Yingjuan, additional, Yang, Gong-She, additional, Johnson, Danielle E., additional, Backer, Jonathan M., additional, Pessin, Jeffrey E., additional, and Zong, Haihong, additional
- Published
- 2014
- Full Text
- View/download PDF
12. CytochromeP-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance
- Author
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Zong, Haihong, primary, Armoni, Michal, additional, Harel, Chava, additional, Karnieli, Eddy, additional, and Pessin, Jeffrey E., additional
- Published
- 2012
- Full Text
- View/download PDF
13. High basal cell surface levels of fish GLUT4 are related to reduced sensitivity of insulin-induced translocation toward GGA and AS160 inhibition in adipocytes
- Author
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Capilla, Encarnación, primary, Díaz, Mònica, additional, Hou, June Chunqiu, additional, Planas, Josep V., additional, and Pessin, Jeffrey E., additional
- Published
- 2010
- Full Text
- View/download PDF
14. Suppression of mTORC1 activation in acid-α-glucosidase-deficient cells and mice is ameliorated by leucine supplementation.
- Author
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Adi Shemesh, Yichen Wang, Yingjuan Yang, Gong-She Yang, Johnson, Danielle E., Backer, Jonathan M., Pessin, Jeffrey E., and Haihong Zong
- Subjects
IMMUNOSUPPRESSION ,TOR proteins ,GLUCOSIDASES ,LEUCINE ,WASTING syndrome ,GLYCOGEN storage disease type II - Abstract
Pompe disease is due to a deficiency in acid-α-glucosidase (GAA) and results in debilitating skeletal muscle wasting, characterized by the accumulation of glycogen and autophagic vesicles. Given the role of lysosomes as a platform for mTORC1 activation, we examined mTORC1 activity in models of Pompe disease. GAA-knockdown C2C12 myoblasts and GAA-deficient human skin fibroblasts of infantile Pompe patients were found to have decreased mTORC1 activation. Treatment with the cell-permeable leucine analog L-leucyl-L-leucine methyl ester restored mTORC1 activation. In vivo, Pompe mice also displayed reduced basal and leucine-stimulated mTORC1 activation in skeletal muscle, whereas treatment with a combination of insulin and leucine normalized mTORC1 activation. Chronic leucine feeding restored basal and leucine-stimulated mTORC1 activation, while partially protecting Pompe mice from developing kyphosis and the decline in muscle mass. Leucine-treated Pompe mice showed increased spontaneous activity and running capacity, with reduced muscle protein breakdown and glycogen accumulation. Together, these data demonstrate that GAA deficiency results in reduced mTORC1 activation that is partly responsible for the skeletal muscle wasting phenotype. Moreover, mTORC1 stimulation by dietary leucine supplementation prevented some of the detrimental skeletal muscle dysfunction that occurs in the Pompe disease mouse model. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
15. Adenovirus-mediated transfer of a modified human proinsulin gene reverses hyperglycemia in diabetic mice
- Author
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Short, Daniel K., primary, Okada, Shuichi, additional, Yamauchi, Keishi, additional, and Pessin, Jeffrey E., additional
- Published
- 1998
- Full Text
- View/download PDF
16. Regulation of glucose transporters GLUT-4 and GLUT-1 gene transcription in denervated skeletal muscle
- Author
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Jones, Jared P., primary, Tapscott, Edward B., additional, Olson, Ann Louise, additional, Pessin, Jeffrey E., additional, and Dohm, G. Lynis, additional
- Published
- 1998
- Full Text
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17. Cytochrome P-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance.
- Author
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Haihong Zong, Armoni, Michal, Harel, Chava, Karnieli, Eddy, and Pessin, Jeffrey E.
- Abstract
Conventional (whole body) CYP2E1 knockout mice displayed protection against high-fat dietinduced weight gain, obesity, and hyperlipidemia with increased energy expenditure despite normal food intake and spontaneous locomotor activity. In addition, the CYP2E1 knockout mice displayed a marked improvement in glucose tolerance on both normal chow and high-fat diets. Euglycemic-hyperinsulinemic clamps demonstrated a marked protection against high-fat diet-induced insulin resistance in CYP2E1 knockout mice, with enhanced adipose tissue glucose uptake and insulin suppression of hepatic glucose output. In parallel, adipose tissue was protected against high-fat diet-induced proinflammatory cytokine production. Taken together, these data demonstrate that the CYP2E1 deletion protects mice against high-fat diet-induced insulin resistance with improved glucose homeostasis in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
18. Initial entry of IRAP into the insulin-responsive storage compartment occurs prior to basal or insulin-stimulated plasma membrane recycling.
- Author
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Gang Liu, June Chunqiu Hou, Watson, Robert T., and Pessin, Jeffrey E.
- Subjects
AMINOPEPTIDASES ,INULIN ,BIOSYNTHESIS ,PEPTIDASE ,PROTEINASES ,BIOCHEMICAL engineering ,ENDOCRINOLOGY - Abstract
To examine the acquisition of insulin sensitivity after the initial biosynthesis of the insulin-responsive aminopeptidase (IRAP), 3T3 L1 adipocytes were transfected with an enhanced green fluorescent protein-IRAP (EGFP-IRAP) fusion protein. In the absence of insulin, IRAP was rapidly localized (1 3 h) to secretory membranes and retained in these intracellular membrane compartments with little accumulation at the plasma membrane. However, insulin was unable to induce translocation to the plasma membrane until 64 h after biosynthesis. This was in marked contrast to another type 11 membrane protein (syntaxin 3) that rapidly defaulted to the plasma membrane 3 h after expression. In parallel with the time-dependent acquisition of insulin responsiveness, the newly synthesized IRAP protein converted from a brefeldin A-sensitive to a brefeldin A-insensitive state. The initial trafficking of IRAP to the insulin-responsive compartment was independent of plasma membrane endocytosis, as expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis but had no effect on the insulin-stimulated translocation of the newly synthesized IRAP protein. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
19. Abundance, localization, and insulin-induced translocation of glucose transporters in red and white muscle.
- Author
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MARETTE, ANDRÉ, RICHARDSON, JEANNE M., RAMLAL, TOOLSIE, BALON, THOMAS W., VRANIC, MLADEN, PESSIN, JEFFREY E., and KLIP, AMIRA
- Published
- 1992
- Full Text
- View/download PDF
20. Suppression of mTORC1 activation in acid-α-glucosidase-deficient cells and mice is ameliorated by leucine supplementation.
- Author
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Shemesh A, Wang Y, Yang Y, Yang GS, Johnson DE, Backer JM, Pessin JE, and Zong H
- Subjects
- Animals, Cell Line, Disease Models, Animal, Dose-Response Relationship, Drug, Fibroblasts drug effects, Fibroblasts enzymology, Glycogen metabolism, Glycogen Storage Disease Type II enzymology, Glycogen Storage Disease Type II genetics, Glycogen Storage Disease Type II pathology, Glycogen Storage Disease Type II physiopathology, Humans, Insulin pharmacology, Kyphosis enzymology, Kyphosis pathology, Kyphosis physiopathology, Kyphosis prevention & control, Lysosomes drug effects, Lysosomes enzymology, Mechanistic Target of Rapamycin Complex 1, Mice, Inbred C57BL, Mice, Knockout, Motor Activity drug effects, Muscle, Skeletal enzymology, Muscle, Skeletal pathology, Muscle, Skeletal physiopathology, Muscular Atrophy enzymology, Muscular Atrophy pathology, Muscular Atrophy physiopathology, Muscular Atrophy prevention & control, Myoblasts drug effects, Myoblasts enzymology, RNA Interference, Transfection, alpha-Glucosidases genetics, Dietary Supplements, Dipeptides pharmacology, Glycogen Storage Disease Type II drug therapy, Multiprotein Complexes metabolism, Muscle, Skeletal drug effects, TOR Serine-Threonine Kinases metabolism, alpha-Glucosidases deficiency
- Abstract
Pompe disease is due to a deficiency in acid-α-glucosidase (GAA) and results in debilitating skeletal muscle wasting, characterized by the accumulation of glycogen and autophagic vesicles. Given the role of lysosomes as a platform for mTORC1 activation, we examined mTORC1 activity in models of Pompe disease. GAA-knockdown C2C12 myoblasts and GAA-deficient human skin fibroblasts of infantile Pompe patients were found to have decreased mTORC1 activation. Treatment with the cell-permeable leucine analog L-leucyl-L-leucine methyl ester restored mTORC1 activation. In vivo, Pompe mice also displayed reduced basal and leucine-stimulated mTORC1 activation in skeletal muscle, whereas treatment with a combination of insulin and leucine normalized mTORC1 activation. Chronic leucine feeding restored basal and leucine-stimulated mTORC1 activation, while partially protecting Pompe mice from developing kyphosis and the decline in muscle mass. Leucine-treated Pompe mice showed increased spontaneous activity and running capacity, with reduced muscle protein breakdown and glycogen accumulation. Together, these data demonstrate that GAA deficiency results in reduced mTORC1 activation that is partly responsible for the skeletal muscle wasting phenotype. Moreover, mTORC1 stimulation by dietary leucine supplementation prevented some of the detrimental skeletal muscle dysfunction that occurs in the Pompe disease mouse model., (Copyright © 2014 the American Physiological Society.)
- Published
- 2014
- Full Text
- View/download PDF
21. Cytochrome P-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance.
- Author
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Zong H, Armoni M, Harel C, Karnieli E, and Pessin JE
- Subjects
- Adipose Tissue, White metabolism, Animals, Biological Transport, Cytochrome P-450 CYP2E1 genetics, Cytokines blood, Fatty Liver etiology, Fatty Liver pathology, Fatty Liver prevention & control, Glucose metabolism, Glucose Intolerance blood, Glucose Intolerance etiology, Glucose Intolerance prevention & control, Hyperlipidemias blood, Hyperlipidemias etiology, Hyperlipidemias prevention & control, Insulin metabolism, Liver metabolism, Liver pathology, Male, Mice, Mice, 129 Strain, Mice, Knockout, Molecular Targeted Therapy, Muscle Fibers, Skeletal metabolism, Obesity etiology, Obesity physiopathology, Obesity prevention & control, Signal Transduction, Cytochrome P-450 CYP2E1 physiology, Diet, High-Fat adverse effects, Insulin Resistance, Obesity metabolism
- Abstract
Conventional (whole body) CYP2E1 knockout mice displayed protection against high-fat diet-induced weight gain, obesity, and hyperlipidemia with increased energy expenditure despite normal food intake and spontaneous locomotor activity. In addition, the CYP2E1 knockout mice displayed a marked improvement in glucose tolerance on both normal chow and high-fat diets. Euglycemic-hyperinsulinemic clamps demonstrated a marked protection against high-fat diet-induced insulin resistance in CYP2E1 knockout mice, with enhanced adipose tissue glucose uptake and insulin suppression of hepatic glucose output. In parallel, adipose tissue was protected against high-fat diet-induced proinflammatory cytokine production. Taken together, these data demonstrate that the CYP2E1 deletion protects mice against high-fat diet-induced insulin resistance with improved glucose homeostasis in vivo.
- Published
- 2012
- Full Text
- View/download PDF
22. High basal cell surface levels of fish GLUT4 are related to reduced sensitivity of insulin-induced translocation toward GGA and AS160 inhibition in adipocytes.
- Author
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Capilla E, Díaz M, Hou JC, Planas JV, and Pessin JE
- Subjects
- 3T3 Cells, Animals, Blood Glucose metabolism, Cell Membrane metabolism, Energy Metabolism, Evolution, Molecular, Gene Expression Regulation, Mice, Protein Isoforms, Rats, Fish Proteins metabolism, Glucose Transporter Type 4 metabolism, Oncorhynchus kisutch metabolism, Protein Transport physiology, Trout metabolism
- Abstract
Glucose entry into cells is mediated by a family of facilitative transporter proteins (GLUTs). In mammals, GLUT4 is expressed in insulin-sensitive tissues and is responsible for the postprandial uptake of glucose. In fish, GLUT4 also mediates insulin-regulated glucose entry into cells but differs from mammalian GLUT4 in its affinity for glucose and in protein motifs known to be important for the traffic of GLUT4. In this study, we have characterized the intracellular and plasma membrane (PM) traffic of two orthologs of GLUT4 in fish, trout (btGLUT4) and salmon (okGLUT4), that do not share the amino terminal FQQI targeting motif of mammalian GLUT4. btGLUT4 (FQHL) and, to a lesser extent, okGLUT4 (FQQL) showed higher basal PM levels, faster traffic to the PM after biosynthesis, and earlier acquisition of insulin responsiveness than rat GLUT4. Furthermore, btGLUT4 showed a similar profile of internalization than rat GLUT4. Expression of the dominant-interfering AS160-4P mutant caused a significant decrease in the insulin-induced PM levels of okGLUT4 and rat GLUT4 and, to a lesser extent, of btGLUT4, suggesting that btGLUT4 has reduced retention into the IRC. Contrary to rat GLUT4 and okGLUT4, the presence of btGLUT4 at the PM under insulin-stimulated conditions was not affected by coexpression of a dominant-interfering GGA mutant. These data suggest that fish GLUT4 follow a different trafficking pathway to the PM compared with rat GLUT4 that seems to be relatively independent of GGA. These results indicate that the regulated trafficking characteristics of GLUT4 have been modified during evolution from fish to mammals.
- Published
- 2010
- Full Text
- View/download PDF
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