PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

González-Rodriguez, Águeda; Nevado, Carmen; Escrivá, Fernando; Sesti, Giorgio; Rondinone, Cristina M.; Benito, Manuel; Valverde, Ángela M.

doi:10.1152/ajpgi.00514.2007

Cited by 20 publications

(14 citation statements)

References 44 publications

(62 reference statements)

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“…To unravel the molecular mechanisms underlying serotonin inhibition of glucose uptake we first examined expression and localization of two major glucose transporters (Gluts) in hepatocytes, Glut1 and Glut2 (Gonzalez-Rodriguez et al, 2008). Serotonin stimulation of hepatocytes isolated from Htr2b fl/fl or Htr2b liver ∆/∆ mice did not alter subcellular localization of these two transporters (Figure 5D) but it decreased Glut2 abundance since the intensity of the Glut2 staining decreased markedly in serotonin-stimulated WT but not Htr2b -deficient hepatocytes.…”

Section: Resultsmentioning

confidence: 99%

Gut-Derived Serotonin Is a Multifunctional Determinant to Fasting Adaptation

et al. 2012

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Section: Resultsmentioning

confidence: 99%

Gut-Derived Serotonin Is a Multifunctional Determinant to Fasting Adaptation

et al. 2012

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“…Thus, hepatic insulin sensitivity caused by PTP1B deficiency is acquired through postnatal development (Gonzá lez-Rodriguez et al 2007). Thus, the lack of PTP1B increased the net free intrahepatic glucose levels in vivo and the glucose uptake in neonatal hepatocytes, which may account for the hypoglycaemic phenotype observed in the knockout mice (Gonzalez-Rodriguez et al 2008).…”

Section: Ptp1b and Irs-2 Play A Major Role In Insulin Action And Inacmentioning

confidence: 98%

“…Thus, PTP1B is an important negative regulator of insulin signalling. Thus, the lack of PTP1B increased the net free intrahepatic glucose levels in vivo and the glucose uptake in neonatal hepatocytes, which may account for the hypoglycaemic phenotype observed in the knockout mice (Gonzalez-Rodriguez et al 2008). Yet, the lack of PTP1B in adult hepatocytes increased insulin sensitivity.…”

Section: Ptp1b and Irs-2 Play A Major Role In Insulin Action And Inacmentioning

confidence: 99%

Tissue specificity on insulin action and resistance: past to recent mechanisms

Benito

2011

Acta Physiologica

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Insulin resistance is the most important pathophysiological feature in many pre-diabetic states. Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion by pancreatic β-cells. The creation of monogenic or polygenic genetically manipulated mice models in a tissue-specific manner was of great help to elucidate the tissue specificity of insulin action and its contribution to the overall insulin resistance. However, a complete understanding of the molecular bases of insulin action and resistance requires the identification of intracellular pathways that regulate insulin-stimulated proliferation, differentiation and metabolism. Accordingly, cell lines derived from insulin target tissues such as brown adipose tissue, liver and beta islets lacking insulin resistance or sensitive candidate genes such as IRS-1, IRS-2, IRS-3, IR and PTP1B have been developed. Indeed, these cell lines have also been very useful to understand the tissue specificity of insulin action and inaction. Obesity is a risk factor for several components of the metabolic syndromes such as type 2 diabetes, dyslipidaemia and systolic hypertension, because white and brown adipose tissues as endocrine organs express and secrete a variety of adipocytokines that can act at both local and systemic levels, modulating the insulin sensitivity. Recent studies revealed that the subjects with the highest transcription rates of genes encoding TNF-α and IL-6 were prone to develop obesity, insulin resistance and type 2 diabetes. Accordingly, we specifically focus in this review on the impact of those adipocytokines on the modulation of insulin action in skeletal muscle.

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“…28 Because IRA represents the predominant isoform in proliferative cells, 29 we analyzed the pattern of IR isoforms after PH. Before surgery, adult liver expressed mostly the IRB isoform 28 ( Figure 1F). However, regenerating livers lacking PTP1B re-expressed IRA 24 hours after PH; in PTP1B ϩ/ϩ mice, a slight increase in IRA was detected at 48 hours.…”

Section: Increased Liver/body Weight Ratio and Hepatocyte Proliferatimentioning

confidence: 99%

Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency Accelerates Hepatic Regeneration in Mice

Revuelta-Cervantes

Mayoral

Miranda

et al. 2011

The American Journal of Pathology

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Protein tyrosine phosphatase 1B (PTP1B) is a key regulator of metabolism and cell growth by its ability to dephosphorylate tyrosine kinase receptors and modulate the intensity of their signaling cascades. Because liver regeneration involves tyrosine phosphorylation-mediated signaling, we investigated the role of PTP1B in this process by performing partial hepatectomy in wild-type (PTP1B ؉/؉ ) and PTP1B-deficient (PTP1B ؊/؊ ) mice. The expression of PCNA and cyclins D1 and E (cell proliferation markers) was enhanced in PTP1B ؊/؊ regenerating livers, in parallel with 5=-bromo-2=-deoxyuridine incorporation. Phosphorylation of JNK1/2 and STAT3, early triggers of hepatic regeneration in response to TNF-␣ and IL-6, was accelerated in PTP1B ؊/؊ mice compared with PTP1B ؉/؉ mice. These phosphorylations were increased in PTP1B ؊/؊ hepatocytes or by silencing PTP1B in wild-type cells and decreased further after the addition of recombinant PTP1B. Enhanced EGFand HGF receptor-mediated signaling was observed in regenerating livers lacking PTP1B and in EGF-or HGF-stimulated PTP1B ؊/؊ hepatocytes. Moreover, PTP1B ؊/؊ mice displayed a more rapid increase in intrahepatic lipid accumulation than PTP1B ؉/؉ control mice. Late responses to partial hepatectomy revealed additional divergences because stress-mediated signaling was attenuated at 24 to 96 hours in PTP1B ؊/؊ mice compared with PTP1B ؉/؉ mice. Finally, PTP1B deficiency also improves hepatic regeneration in mice fed a high-fat diet. These results suggest that pharmacological inhibition of PTP1B would improve liver regeneration in patients with acute or chronic liver injury.

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PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

Cited by 20 publications

References 44 publications

Gut-Derived Serotonin Is a Multifunctional Determinant to Fasting Adaptation

Gut-Derived Serotonin Is a Multifunctional Determinant to Fasting Adaptation

Tissue specificity on insulin action and resistance: past to recent mechanisms

Protein Tyrosine Phosphatase 1B (PTP1B) Deficiency Accelerates Hepatic Regeneration in Mice

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