PMID- 32839348
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20210125
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 69
IP  - 11
DP  - 2020 Nov
TI  - Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require 
      AMPK-Induced Txn2 Expression but Are Dispensable for Physiological 
      Counterregulation.
PG  - 2253-2266
LID - 10.2337/db20-0577 [doi]
AB  - The ventromedial nucleus of the hypothalamus (VMN) is involved in the 
      counterregulatory response to hypoglycemia. VMN neurons activated by hypoglycemia 
      (glucose-inhibited [GI] neurons) have been assumed to play a critical although 
      untested role in this response. Here, we show that expression of a dominant 
      negative form of AMPK or inactivation of AMPK alpha1 and alpha2 subunit genes in Sf1 
      neurons of the VMN selectively suppressed GI neuron activity. We found that Txn2, 
      encoding a mitochondrial redox enzyme, was strongly downregulated in the absence 
      of AMPK activity and that reexpression of Txn2 in Sf1 neurons restored GI neuron 
      activity. In cell lines, Txn2 was required to limit glucopenia-induced reactive 
      oxygen species production. In physiological studies, absence of GI neuron 
      activity after AMPK suppression in the VMN had no impact on the counterregulatory 
      hormone response to hypoglycemia or on feeding. Thus, AMPK is required for GI 
      neuron activity by controlling the expression of the antioxidant enzyme Txn2. 
      However, the glucose-sensing capacity of VMN GI neurons is not required for the 
      normal counterregulatory response to hypoglycemia. Instead, it may represent a 
      fail-safe system in case of impaired hypoglycemia sensing by peripherally located 
      glucose detection systems that are connected to the VMN.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Quenneville, Simon
AU  - Quenneville S
AD  - Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
FAU - Labouebe, Gwenael
AU  - Labouebe G
AD  - Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
FAU - Basco, Davide
AU  - Basco D
AD  - Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
FAU - Metref, Salima
AU  - Metref S
AD  - Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
FAU - Viollet, Benoit
AU  - Viollet B
AD  - Universite de Paris, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Foretz, Marc
AU  - Foretz M
AD  - Universite de Paris, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Thorens, Bernard
AU  - Thorens B
AUID- ORCID: 0000-0002-3738-0129
AD  - Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland 
      bernard.thorens@unil.ch.
LA  - eng
SI  - figshare/10.2337/figshare.12827294
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200824
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Txn2 protein, mouse)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 2.7.11.1 (AMPK alpha1 subunit, mouse)
RN  - EC 2.7.11.1 (AMPK alpha2 subunit, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Blood Glucose
MH  - Cells, Cultured
MH  - Glucose/*metabolism
MH  - Humans
MH  - Hypoglycemia/*blood
MH  - Neurons/*physiology
MH  - Patch-Clamp Techniques
MH  - Thioredoxins/genetics/*metabolism
MH  - Ventromedial Hypothalamic Nucleus/*cytology
PMC - PMC7576557
EDAT- 2020/08/26 06:00
MHDA- 2021/01/26 06:00
PMCR- 2020/08/24
CRDT- 2020/08/26 06:00
PHST- 2020/05/28 00:00 [received]
PHST- 2020/08/18 00:00 [accepted]
PHST- 2020/08/26 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
PHST- 2020/08/26 06:00 [entrez]
PHST- 2020/08/24 00:00 [pmc-release]
AID - db20-0577 [pii]
AID - 200577 [pii]
AID - 10.2337/db20-0577 [doi]
PST - ppublish
SO  - Diabetes. 2020 Nov;69(11):2253-2266. doi: 10.2337/db20-0577. Epub 2020 Aug 24.