PMID- 23782941
OWN - NLM
STAT- MEDLINE
DCOM- 20131112
LR  - 20211021
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 154
IP  - 9
DP  - 2013 Sep
TI  - Leptin action in the ventromedial hypothalamic nucleus is sufficient, but not 
      necessary, to normalize diabetic hyperglycemia.
PG  - 3067-76
LID - 10.1210/en.2013-1328 [doi]
AB  - In rodent models of type 1 diabetes, leptin administration into brain ventricles 
      normalizes blood glucose at doses that have no effect when given peripherally. 
      The ventromedial nucleus of the hypothalamus (VMN) is a potential target for 
      leptin's antidiabetic effects because leptin-sensitive neurons in this brain area 
      are implicated in glucose homeostasis. To test this hypothesis, we injected 
      leptin directly into the bilateral VMN of rats with streptozotocin-induced 
      uncontrolled diabetes mellitus. This intervention completely normalized both 
      hyperglycemia and the elevated rates of hepatic glucose production and plasma 
      glucagon levels but had no effect on tissue glucose uptake in the skeletal muscle 
      or brown adipose tissue as measured using tracer dilution techniques during a 
      basal clamp. To determine whether VMN leptin signaling is required for 
      leptin-mediated normalization of diabetic hyperglycemia, we studied mice in which 
      the leptin receptor gene was deleted in VMN steroidogenic factor 1 neurons using 
      cre-loxP technology. Our findings indicate leptin action within these neurons is 
      not required for the correction of diabetic hyperglycemia by central leptin 
      infusion. We conclude that leptin signaling in the VMN is sufficient to mediate 
      leptin's antidiabetic action but may not be necessary for this effect. Leptin 
      action within a distributed neuronal network may mediate its effects on glucose 
      homeostasis.
FAU - Meek, Thomas H
AU  - Meek TH
AD  - Diabetes and Obesity Center of Excellence, University of Washington at South Lake 
      Union, 850 Republican Street, N334, Box 358055, Seattle, Washington 98195, USA.
FAU - Matsen, Miles E
AU  - Matsen ME
FAU - Dorfman, Mauricio D
AU  - Dorfman MD
FAU - Guyenet, Stephan J
AU  - Guyenet SJ
FAU - Damian, Vincent
AU  - Damian V
FAU - Nguyen, Hong T
AU  - Nguyen HT
FAU - Taborsky, Gerald J Jr
AU  - Taborsky GJ Jr
FAU - Morton, Gregory J
AU  - Morton GJ
LA  - eng
GR  - T32 DK007247/DK/NIDDK NIH HHS/United States
GR  - F32 DK097859/DK/NIDDK NIH HHS/United States
GR  - T32 DK0007247/DK/NIDDK NIH HHS/United States
GR  - R01 DK089056/DK/NIDDK NIH HHS/United States
GR  - R56 DK050154/DK/NIDDK NIH HHS/United States
GR  - DK050154/DK/NIDDK NIH HHS/United States
GR  - DK089053/DK/NIDDK NIH HHS/United States
GR  - R01 DK050154/DK/NIDDK NIH HHS/United States
GR  - P30 DK035816/DK/NIDDK NIH HHS/United States
GR  - DK035816/DK/NIDDK NIH HHS/United States
GR  - P30 DK017047/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130619
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Leptin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Leptin)
RN  - 0 (Recombinant Proteins)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 1/blood/drug therapy/*metabolism/pathology
MH  - Glucagon/blood/metabolism
MH  - Glucagon-Secreting Cells/drug effects/metabolism
MH  - Gluconeogenesis/drug effects
MH  - Hyperglycemia/*prevention & control
MH  - Hypoglycemic Agents/administration & dosage/metabolism/therapeutic use
MH  - Infusions, Intraventricular
MH  - Injections, Intraventricular
MH  - Leptin/administration & dosage/genetics/*metabolism/therapeutic use
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/agonists/genetics/metabolism
MH  - Neurons/drug effects/*metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Leptin/agonists/genetics/*metabolism
MH  - Recombinant Proteins/administration & dosage/metabolism/therapeutic use
MH  - *Signal Transduction/drug effects
MH  - Ventromedial Hypothalamic Nucleus/drug effects/*metabolism/pathology
PMC - PMC3749482
EDAT- 2013/06/21 06:00
MHDA- 2013/11/13 06:00
PMCR- 2014/09/01
CRDT- 2013/06/21 06:00
PHST- 2013/06/21 06:00 [entrez]
PHST- 2013/06/21 06:00 [pubmed]
PHST- 2013/11/13 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - en.2013-1328 [pii]
AID - EN-13-1328 [pii]
AID - 10.1210/en.2013-1328 [doi]
PST - ppublish
SO  - Endocrinology. 2013 Sep;154(9):3067-76. doi: 10.1210/en.2013-1328. Epub 2013 Jun 
      19.