Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis

Pardini, Aaron W.; Nguyen, Hong T.; Figlewicz, Dianne P.; Baskin, Denis G.; Williams, D.B.; Kim, Francis; Schwartz, Michael W.

doi:10.1016/j.brainres.2006.06.109

Cited by 84 publications

(50 citation statements)

References 37 publications

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“…Considering the involvement of insulin in cognitive and motivational processes that depend on DA neurotransmission, insulin receptors and their downstream substrates (IRS-2 and PI3K) in rat brain are densely expressed in DA neurons within the ventral tegmental area (VTA) and activation of these receptors enhances PI3K activity and DAT mRNA expression (Figlewicz et al, 1994;Pardini et al, 2006;Figlewicz and Benoit, 2009). Moreover, insulin receptor activation appeared to increase the surface expression and function of DAT in rat striatum, enhancing DA reuptake in a P13K-dependent manner (Patterson et al, 1998;Carvelli et al, 2002;Garcia et al, 2005;Lute et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

et al. 2011

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Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [ 3 H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [ 3 H]norepinephrine in nucleus accumbens slices, but not on that of [ 3 H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocainesensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.

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Section: Discussionmentioning

confidence: 99%

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

et al. 2011

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“…However, substrates involved in mediating these effects are still unknown. It has been recently shown that brain IRS-2 null mice exhibited abnormal neuron development and brain growth (Schubert et al 2003) and it is predominantly distributed in brain areas regulating energy homeostasis (Pardini et al 2006). Also, STAT-3 is known to maintain neural precursor cells in the mouse embryonic neocortex (Yoshimatsu et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic alterations in fetuses of high fat diet-fed obese female rats

Gupta¹,

Srinivasan²,

Thamadilok³

et al. 2008

Journal of Endocrinology

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The offspring of high fat (HF) diet-fed rats display increased body weight during adulthood. However, it is not known whether the changes in appetite regulation in these animals occur in utero or postnatally. We investigated the effects of maternal obesity induced by a HF diet prior to and during pregnancy on leptin and insulin signaling and the expression of orexigenic and anorexigenic peptides in term fetal hypothalami. The consumption of a HF diet prior to and during pregnancy resulted in obesity in HF female rats; additionally, HF female rats exhibited hyperinsulinemia and hyperleptinemia which were exaggerated in late gestation compared with control female rats that were fed a standard rodent laboratory chow (LC). Term fetuses of HF female rats (FHF) also had significantly higher serum leptin and insulin levels compared with control fetuses (FLC) while there was no difference in average fetal weight between the two groups.FHF hypothalami showed elevated levels of mRNA and proteins for leptin long receptor and insulin receptor bsubunit. However, the protein levels of signal transducers and activators of transcription-3 and insulin receptor substrate-2, the downstream signaling components of leptin and insulin signaling respectively were decreased. Also, FHF hypothalami had increased mRNA levels of neuropeptide Y and agoutirelated polypeptide indicating that orexigenic neuropeptides in HF progeny are already upregulated by term fetal stage. Additionally, the mRNA levels of pro-opiatemelanocortin and melanocortin receptor-4 were also increased in the HF fetal hypothalami. These findings indicate potential programming effects of an altered intrauterine environment induced by HF diet consumption on appetite-regulating neuropeptides and leptin and insulin signaling in the late fetal period.

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“…Although in theory, the absence of IRS proteins cannot distinguish between insulin/IGFs (IIS) or several other intercellular signals modulating them, and the lack of IGF-I receptors cannot discriminate the source of IGF-I (whether serum or brain), their phenotypes help clarify the role of IGF-I in the brain. Collectively, these studies suggest a major role for IRS-2 in IIS brain signaling (Pardini et al, 2006), while the role of IRS-1 is less evident. They also confirm a key role of IGF-I in normal brain postnatal growth (Liu et al, 2009) as well as an important action on neuroendocrine loops (Kappeler et al, 2008a) or amyloidosis (Freude et al, 2009).…”

Section: Brain Igf-i and The Brain Insulin Family Of Peptidesmentioning

confidence: 86%

Toward a comprehensive neurobiology of IGF‐I

Torres‐Alemán

2010

Developmental Neurobiology

151

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Imatinib is the drug of first choice for most patients with chronic phase chronic myeloid leukemia (CML). Although it is generally well tolerated, a number of hematological and nonhematological side‐effects have been described. We report here that imatinib induces hypophosphatemia in a high proportion of our series of CML patients previously treated with interferon α, and that this previously unreported side effect is associated with response. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.

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Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis

Cited by 84 publications

References 37 publications

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

Insulin Modulates Cocaine-Sensitive Monoamine Transporter Function and Impulsive Behavior

Hypothalamic alterations in fetuses of high fat diet-fed obese female rats

Toward a comprehensive neurobiology of IGF‐I

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