1999
DOI: 10.1126/science.283.5407.1544
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Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene

Abstract: Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed incre… Show more

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Cited by 2,031 publications
(1,620 citation statements)
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References 19 publications
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“…19,20,53 In this study, we show protection against the development of hepatic steatosis together with improved regenerative responses in PTP1B Ϫ/Ϫ mice fed an HFD before PH. In addition to the protection against insulin resistance and obesity, 20,54 an additional benefit of PTP1B deficiency may be the improvement of liver regeneration under conditions of increased lipid intake, as demonstrated herein by accelerated or increased induction of S-phase markers and an increased hepatosomal index compared with wild-type controls.…”
Section: Discussionsupporting
confidence: 53%
See 1 more Smart Citation
“…19,20,53 In this study, we show protection against the development of hepatic steatosis together with improved regenerative responses in PTP1B Ϫ/Ϫ mice fed an HFD before PH. In addition to the protection against insulin resistance and obesity, 20,54 an additional benefit of PTP1B deficiency may be the improvement of liver regeneration under conditions of increased lipid intake, as demonstrated herein by accelerated or increased induction of S-phase markers and an increased hepatosomal index compared with wild-type controls.…”
Section: Discussionsupporting
confidence: 53%
“…18 Extensive analysis of the PTP1B-deficient (PTP1B Ϫ/Ϫ ) mice has confirmed that the IR is a key physiological target of PTP1B. 19,20 In fact, PTP1B inhibition is actually being assayed as a potential therapy for type 2 diabetes mellitus. Despite the negative modulation of activation of receptors of the tyrosine kinase superfamily by PTP1B, PTP1B Ϫ/Ϫ mice lack any obvious signs of increased activity of these receptors, such as susceptibility to tumor development through life.…”
mentioning
confidence: 99%
“…Insulin receptor antibody is polyconal rabbit antihuman antipeptide (Santa Cruz Biotechnology, Santa Cruz, CA) 18. Goat polyclonal p‐insulin Rβ antibody (Santa Cruz Biotechnology) was used as the phosphorylated insulin receptor antibody.…”
Section: Methodsmentioning
confidence: 99%
“…G-6-Pase catalyzes the terminal reaction of glycogenolysis. GSK-3 is reported to play an important role in the regulation of glycogen synthesis via inhibitory phosphorylation of glycogen synthase [12], and PTP1B is implicated as a negative regulator of insulin signaling [13]. As shown in Table 3, FR258900 inhibited glycogen phosphorylase with IC 50 of 2.5 mM.…”
Section: Physico-chemical Propertiesmentioning
confidence: 95%