PMID- 22688333
OWN - NLM
STAT- MEDLINE
DCOM- 20121105
LR  - 20221207
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 61
IP  - 9
DP  - 2012 Sep
TI  - Pulsatile portal vein insulin delivery enhances hepatic insulin action and 
      signaling.
PG  - 2269-79
LID - 10.2337/db11-1462 [doi]
AB  - Insulin is secreted as discrete insulin secretory bursts at ~5-min intervals into 
      the hepatic portal vein, these pulses being attenuated early in the development 
      of type 1 and type 2 diabetes mellitus (T2DM). Intraportal insulin infusions 
      (pulsatile, constant, or reproducing that in T2DM) indicated that the pattern of 
      pulsatile insulin secretion delivered via the portal vein is important for 
      hepatic insulin action and, therefore, presumably for hepatic insulin signaling. 
      To test this, we examined hepatic insulin signaling in rat livers exposed to the 
      same three patterns of portal vein insulin delivery by use of sequential liver 
      biopsies in anesthetized rats. Intraportal delivery of insulin in a constant 
      versus pulsatile pattern led to delayed and impaired activation of hepatic 
      insulin receptor substrate (IRS)-1 and IRS-2 signaling, impaired activation of 
      downstream insulin signaling effector molecules AKT and Foxo1, and decreased 
      expression of glucokinase (Gck). We further established that hepatic Gck 
      expression is decreased in the HIP rat model of T2DM, a defect that correlated 
      with a progressive defect of pulsatile insulin secretion. We conclude that the 
      physiological pulsatile pattern of insulin delivery is important in hepatic 
      insulin signaling and glycemic control. Hepatic insulin resistance in diabetes is 
      likely in part due to impaired pulsatile insulin secretion.
FAU - Matveyenko, Aleksey V
AU  - Matveyenko AV
AD  - Larry Hillblom Islet Research Center, Division of Endocrinology, David Geffen 
      School of Medicine, University of California Los Angeles, Los Angeles, 
      California, USA.
FAU - Liuwantara, David
AU  - Liuwantara D
FAU - Gurlo, Tatyana
AU  - Gurlo T
FAU - Kirakossian, David
AU  - Kirakossian D
FAU - Dalla Man, Chiara
AU  - Dalla Man C
FAU - Cobelli, Claudio
AU  - Cobelli C
FAU - White, Morris F
AU  - White MF
FAU - Copps, Kyle D
AU  - Copps KD
FAU - Volpi, Elena
AU  - Volpi E
FAU - Fujita, Satoshi
AU  - Fujita S
FAU - Butler, Peter C
AU  - Butler PC
LA  - eng
GR  - K01 DK089003/DK/NIDDK NIH HHS/United States
GR  - R01 DK098655/DK/NIDDK NIH HHS/United States
GR  - DK-059579/DK/NIDDK NIH HHS/United States
GR  - F32 DK078496/DK/NIDDK NIH HHS/United States
GR  - P30 AG024832/AG/NIA NIH HHS/United States
GR  - R01 DK038712/DK/NIDDK NIH HHS/United States
GR  - R01 DK059579/DK/NIDDK NIH HHS/United States
GR  - P30-AG-024832/AG/NIA NIH HHS/United States
GR  - DK-089003/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 - 20120611
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Foxo1 protein, rat)
RN  - EC 2.7.1.2 (Glucokinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
CIN - Diabetes. 2012 Sep;61(9):2228-9. PMID: 22923651
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Dogs
MH  - Forkhead Transcription Factors/metabolism
MH  - Glucokinase/metabolism
MH  - Insulin/administration & dosage/metabolism/*physiology
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Insulin Resistance/physiology
MH  - Insulin Secretion
MH  - Liver/*physiology
MH  - Male
MH  - Nerve Tissue Proteins/metabolism
MH  - Portal Vein
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
PMC - PMC3425431
EDAT- 2012/06/13 06:00
MHDA- 2012/11/06 06:00
PMCR- 2013/09/01
CRDT- 2012/06/13 06:00
PHST- 2012/06/13 06:00 [entrez]
PHST- 2012/06/13 06:00 [pubmed]
PHST- 2012/11/06 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - db11-1462 [pii]
AID - 1462 [pii]
AID - 10.2337/db11-1462 [doi]
PST - ppublish
SO  - Diabetes. 2012 Sep;61(9):2269-79. doi: 10.2337/db11-1462. Epub 2012 Jun 11.