PMID- 25470549
OWN - NLM
STAT- MEDLINE
DCOM- 20150915
LR  - 20211110
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 20
IP  - 6
DP  - 2014 Dec 2
TI  - A parabrachial-hypothalamic cholecystokinin neurocircuit controls 
      counterregulatory responses to hypoglycemia.
PG  - 1030-7
LID - S1550-4131(14)00503-8 [pii]
LID - 10.1016/j.cmet.2014.11.006 [doi]
AB  - Hypoglycemia engenders an autonomically mediated counterregulatory (CR)-response 
      that stimulates endogenous glucose production to maintain concentrations within 
      an appropriate physiological range. Although the involvement of the brain in 
      preserving normoglycemia has been established, the neurocircuitry underlying 
      centrally mediated CR-responses remains unclear. Here we demonstrate that lateral 
      parabrachial nucleus cholecystokinin (CCK(LPBN)) neurons are a population of 
      glucose-sensing cells (glucose inhibited) with counterregulatory capacity. 
      Furthermore, we reveal that steroidogenic-factor 1 (SF1)-expressing neurons of 
      the ventromedial nucleus of the hypothalamus (SF1(VMH)) are the specific target 
      of CCK(LPBN) glucoregulatory neurons. This discrete CCK(LPBN)-->SF1(VMH) 
      neurocircuit is both necessary and sufficient for the induction of CR-responses. 
      Together, these data identify CCK(LPBN) neurons, and specifically CCK 
      neuropeptide, as glucoregulatory and provide significant insight into the 
      homeostatic mechanisms controlling CR-responses to hypoglycemia.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Garfield, Alastair S
AU  - Garfield AS
AD  - Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, 
      Edinburgh, EH8 9XD, UK; Division of Endocrinology, Diabetes and Metabolism, 
      Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical 
      School, Boston, MA 02115, USA. Electronic address: agarfiel@bidmc.harvard.edu.
FAU - Shah, Bhavik P
AU  - Shah BP
AD  - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth 
      Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
FAU - Madara, Joseph C
AU  - Madara JC
AD  - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth 
      Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
FAU - Burke, Luke K
AU  - Burke LK
AD  - Department of Medicine and Wellcome Trust/Medical Research Council Institute of 
      Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK; Rowett 
      Institute of Nutrition and Health, University of Aberdeen, Aberdeen, AB25 2ZD, 
      UK.
FAU - Patterson, Christa M
AU  - Patterson CM
AD  - Division of Metabolism, Endocrinology, and Diabetes, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
FAU - Flak, Jonathan
AU  - Flak J
AD  - Division of Metabolism, Endocrinology, and Diabetes, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
FAU - Neve, Rachael L
AU  - Neve RL
AD  - Picower Institute for Learning and Memory, Department of Brain and Cognitive 
      Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
FAU - Evans, Mark L
AU  - Evans ML
AD  - Department of Medicine and Wellcome Trust/Medical Research Council Institute of 
      Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, UK.
FAU - Lowell, Bradford B
AU  - Lowell BB
AD  - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth 
      Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
FAU - Myers, Martin G Jr
AU  - Myers MG Jr
AD  - Division of Metabolism, Endocrinology, and Diabetes, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, MI 48105, USA.
FAU - Heisler, Lora K
AU  - Heisler LK
AD  - Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, AB25 
      2ZD, UK.
LA  - eng
GR  - R01 DK089044/DK/NIDDK NIH HHS/United States
GR  - DK059637/DK/NIDDK NIH HHS/United States
GR  - DK020593/DK/NIDDK NIH HHS/United States
GR  - R01 DK098853/DK/NIDDK NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - R01 DK075632/DK/NIDDK NIH HHS/United States
GR  - U24 DK059637/DK/NIDDK NIH HHS/United States
GR  - R01 DK096010/DK/NIDDK NIH HHS/United States
GR  - R37 DK053477/DK/NIDDK NIH HHS/United States
GR  - R01 DK071051/DK/NIDDK NIH HHS/United States
GR  - 098012/WT_/Wellcome Trust/United Kingdom
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Blood Glucose)
RN  - 9011-97-6 (Cholecystokinin)
SB  - IM
CIN - Cell Metab. 2014 Dec 2;20(6):933-5. PMID: 25470543
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Cholecystokinin/*metabolism
MH  - Hypoglycemia/*metabolism
MH  - Hypothalamus/*metabolism
MH  - Male
MH  - Mice
MH  - Parabrachial Nucleus/cytology
PMC - PMC4261079
EDAT- 2014/12/04 06:00
MHDA- 2015/09/16 06:00
PMCR- 2014/12/02
CRDT- 2014/12/04 06:00
PHST- 2014/07/08 00:00 [received]
PHST- 2014/09/29 00:00 [revised]
PHST- 2014/11/07 00:00 [accepted]
PHST- 2014/12/04 06:00 [entrez]
PHST- 2014/12/04 06:00 [pubmed]
PHST- 2015/09/16 06:00 [medline]
PHST- 2014/12/02 00:00 [pmc-release]
AID - S1550-4131(14)00503-8 [pii]
AID - 10.1016/j.cmet.2014.11.006 [doi]
PST - ppublish
SO  - Cell Metab. 2014 Dec 2;20(6):1030-7. doi: 10.1016/j.cmet.2014.11.006.