PMID- 31072002 OWN - NLM STAT- MEDLINE DCOM- 20200106 LR - 20200309 IS - 2073-4425 (Print) IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 10 IP - 5 DP - 2019 May 8 TI - Dissecting the Brain/Islet Axis in Metabesity. LID - 10.3390/genes10050350 [doi] LID - 350 AB - The high prevalence of type 2 diabetes mellitus (T2DM), together with the fact that current treatments are only palliative and do not avoid major secondary complications, reveals the need for novel approaches to treat the cause of this disease. Efforts are currently underway to identify therapeutic targets implicated in either the regeneration or re-differentiation of a functional pancreatic islet beta-cell mass to restore insulin levels and normoglycemia. However, T2DM is not only caused by failures in beta-cells but also by dysfunctions in the central nervous system (CNS), especially in the hypothalamus and brainstem. Herein, we review the physiological contribution of hypothalamic neuronal and glial populations, particularly astrocytes, in the control of the systemic response that regulates blood glucose levels. The glucosensing capacity of hypothalamic astrocytes, together with their regulation by metabolic hormones, highlights the relevance of these cells in the control of glucose homeostasis. Moreover, the critical role of astrocytes in the response to inflammation, a process associated with obesity and T2DM, further emphasizes the importance of these cells as novel targets to stimulate the CNS in response to metabesity (over-nutrition-derived metabolic dysfunctions). We suggest that novel T2DM therapies should aim at stimulating the CNS astrocytic response, as well as recovering the functional pancreatic beta-cell mass. Whether or not a common factor expressed in both cell types can be feasibly targeted is also discussed. FAU - Fuente-Martin, Esther AU - Fuente-Martin E AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. estherdlfuente@gmail.com. FAU - Mellado-Gil, Jose M AU - Mellado-Gil JM AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. jose.mellado@cabimer.es. FAU - Cobo-Vuilleumier, Nadia AU - Cobo-Vuilleumier N AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. nadia.cobo@cabimer.es. FAU - Martin-Montalvo, Alejandro AU - Martin-Montalvo A AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. alejandro.martinmontalvo@cabimer.es. FAU - Romero-Zerbo, Silvana Y AU - Romero-Zerbo SY AUID- ORCID: 0000-0002-6737-992X AD - Instituto de Investigacion Biomedica de Malaga-IBIMA, UGC Endocrinologia y Nutricion. Hospital Regional Universitario de Malaga, 29009 Malaga, Spain. yaniromero@gmail.com. FAU - Diaz Contreras, Irene AU - Diaz Contreras I AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. irene.diaz@cabimer.es. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), 28029 Madrid, Spain. irene.diaz@cabimer.es. FAU - Hmadcha, Abdelkrim AU - Hmadcha A AUID- ORCID: 0000-0002-4105-3702 AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. karim.hmadcha@cabimer.es. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), 28029 Madrid, Spain. karim.hmadcha@cabimer.es. FAU - Soria, Bernat AU - Soria B AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. bernat.soria@cabimer.es. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), 28029 Madrid, Spain. bernat.soria@cabimer.es. FAU - Martin Bermudo, Francisco AU - Martin Bermudo F AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. fmarber@upo.es. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), 28029 Madrid, Spain. fmarber@upo.es. FAU - Reyes, Jose C AU - Reyes JC AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. jose.reyes@cabimer.es. FAU - Bermudez-Silva, Francisco J AU - Bermudez-Silva FJ AUID- ORCID: 0000-0003-3133-9691 AD - Instituto de Investigacion Biomedica de Malaga-IBIMA, UGC Endocrinologia y Nutricion. Hospital Regional Universitario de Malaga, 29009 Malaga, Spain. javier.bermudez@ibima.eu. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), 28029 Madrid, Spain. javier.bermudez@ibima.eu. FAU - Lorenzo, Petra I AU - Lorenzo PI AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. petra.lorenzo@cabimer.es. FAU - Gauthier, Benoit R AU - Gauthier BR AUID- ORCID: 0000-0001-8146-7486 AD - Andalusian Center of Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, 41092 Seville, Spain. benoit.gauthier@cabimer.es. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), 28029 Madrid, Spain. benoit.gauthier@cabimer.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190508 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Astrocytes/metabolism MH - Brain/*metabolism MH - Energy Metabolism MH - Glucose/*metabolism MH - Homeostasis MH - Humans MH - Islets of Langerhans/*metabolism MH - Metabolic Diseases/*metabolism PMC - PMC6562925 OTO - NOTNLM OT - T2DM OT - astrocytes OT - inflammation OT - metabesity OT - obesity OT - pancreatic islet COIS- The authors declare no conflicts of interest. EDAT- 2019/05/11 06:00 MHDA- 2019/05/11 06:01 PMCR- 2019/05/01 CRDT- 2019/05/11 06:00 PHST- 2019/04/10 00:00 [received] PHST- 2019/05/02 00:00 [revised] PHST- 2019/05/02 00:00 [accepted] PHST- 2019/05/11 06:00 [entrez] PHST- 2019/05/11 06:00 [pubmed] PHST- 2019/05/11 06:01 [medline] PHST- 2019/05/01 00:00 [pmc-release] AID - genes10050350 [pii] AID - genes-10-00350 [pii] AID - 10.3390/genes10050350 [doi] PST - epublish SO - Genes (Basel). 2019 May 8;10(5):350. doi: 10.3390/genes10050350.