Ca\(^{2+}\)/Calmodulin-Dependent Protein Kinase Kinase Is Not Involved in Hypothalamic AMP-Activated Protein Kinase Activation by Neuroglucopenia

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Ca\(^{2+}\)/Calmodulin-Dependent Protein Kinase Kinase Is Not Involved in Hypothalamic AMP-Activated Protein Kinase Activation by Neuroglucopenia

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Title: Ca\(^{2+}\)/Calmodulin-Dependent Protein Kinase Kinase Is Not Involved in Hypothalamic AMP-Activated Protein Kinase Activation by Neuroglucopenia
Author: Kawashima, Junji; Alquier, Thierry; Tsuji, Youki; Peroni, Odile Daniele; Kahn, Barbara

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Citation: Kawashima, Junji, Thierry Alquier, Youki Tsuji, Odile D. Peroni, and Barbara B. Kahn. 2012. Ca\(^{2+}\)/calmodulin-dependent protein kinase kinase is not involved in hypothalamic AMP-activated protein kinase activation by neuroglucopenia. PLoS ONE 7(5): e36335.
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Abstract: Hypoglycemia and neuroglucopenia stimulate AMP-activated protein kinase (AMPK) activity in the hypothalamus and this plays an important role in the counterregulatory responses, i.e. increased food intake and secretion of glucagon, corticosterone and catecholamines. Several upstream kinases that activate AMPK have been identified including Ca\(^{2+}\)/Calmodulin-dependent protein kinase kinase (CaMKK), which is highly expressed in neurons. However, the involvement of CaMKK in neuroglucopenia-induced activation of AMPK in the hypothalamus has not been tested. To determine whether neuroglucopenia-induced AMPK activation is mediated by CaMKK, we tested whether STO-609 (STO), a CaMKK inhibitor, would block the effects of 2-deoxy-D-glucose (2DG)-induced neuroglucopenia both ex vivo on brain sections and in vivo. Preincubation of rat brain sections with STO blocked KCl-induced \(\alpha\)1 and \(\alpha\)2-AMPK activation but did not affect AMPK activation by 2DG in the medio-basal hypothalamus. To confirm these findings in vivo, STO was pre-administrated intracerebroventricularly (ICV) in rats 30 min before 2DG ICV injection (40 \(\mu\)mol) to induce neuroglucopenia. 2DG-induced neuroglucopenia lead to a significant increase in glycemia and food intake compared to saline-injected control rats. ICV pre-administration of STO (5, 20 or 50 nmol) did not affect 2DG-induced hyperglycemia and food intake. Importantly, activation of hypothalamic \(\alpha\)1 and \(\alpha\)2-AMPK by 2DG was not affected by ICV pre-administration of STO. In conclusion, activation of hypothalamic AMPK by 2DG-induced neuroglucopenia is not mediated by CaMKK.
Published Version: doi:10.1371/journal.pone.0036335
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349669/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10399830
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