PMID- 28416361
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181113
IS  - 1879-3061 (Electronic)
IS  - 1043-2760 (Print)
IS  - 1043-2760 (Linking)
VI  - 28
IP  - 7
DP  - 2017 Jul
TI  - Unraveling the Regulation of Hepatic Metabolism by Insulin.
PG  - 497-505
LID - S1043-2760(17)30039-5 [pii]
LID - 10.1016/j.tem.2017.03.003 [doi]
AB  - During insulin-resistant states such as type 2 diabetes mellitus (T2DM), insulin 
      fails to suppress hepatic glucose production but promotes lipid synthesis leading 
      to hyperglycemia and hypertriglyceridemia. Defining the downstream signaling 
      pathways underlying the control of hepatic metabolism by insulin is necessary for 
      understanding both normal physiology and the pathogenesis of metabolic disease. 
      We summarize recent literature highlighting the importance of both hepatic and 
      extrahepatic mechanisms in insulin regulation of liver glucose and lipid 
      metabolism. We posit that a failure of insulin to inappropriately regulate liver 
      metabolism during T2DM is not exclusively from an inherent defect in canonical 
      liver insulin signaling but is instead due to a combination of hyperinsulinemia, 
      altered substrate supply, and the input of several extrahepatic signals.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Titchenell, Paul M
AU  - Titchenell PM
AD  - Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at 
      the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: 
      ptitc@mail.med.upenn.edu.
FAU - Lazar, Mitchell A
AU  - Lazar MA
AD  - Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at 
      the University of Pennsylvania, Philadelphia, PA, USA.
FAU - Birnbaum, Morris J
AU  - Birnbaum MJ
AD  - Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at 
      the University of Pennsylvania, Philadelphia, PA, USA; Present address: Internal 
      Medicine, Pfizer Inc., Cambridge, MA, USA. Electronic address: 
      morris.birnbaum@pfizer.com.
LA  - eng
GR  - K01 DK111715/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170414
PL  - United States
TA  - Trends Endocrinol Metab
JT  - Trends in endocrinology and metabolism: TEM
JID - 9001516
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Carbohydrate Metabolism/drug effects
MH  - Glucose/metabolism
MH  - Humans
MH  - Insulin/*pharmacology/physiology
MH  - Insulin Resistance/physiology
MH  - Lipid Metabolism/drug effects
MH  - Lipogenesis/drug effects
MH  - Liver/*metabolism
MH  - Metabolic Networks and Pathways/drug effects
PMC - PMC5477655
MID - NIHMS864354
OTO - NOTNLM
OT  - de novo lipogenesis
OT  - hepatic glucose production
OT  - insulin signaling
OT  - liver metabolism
EDAT- 2017/04/19 06:00
MHDA- 2018/02/27 06:00
PMCR- 2018/07/01
CRDT- 2017/04/19 06:00
PHST- 2016/12/13 00:00 [received]
PHST- 2017/03/15 00:00 [revised]
PHST- 2017/03/23 00:00 [accepted]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2018/07/01 00:00 [pmc-release]
AID - S1043-2760(17)30039-5 [pii]
AID - 10.1016/j.tem.2017.03.003 [doi]
PST - ppublish
SO  - Trends Endocrinol Metab. 2017 Jul;28(7):497-505. doi: 10.1016/j.tem.2017.03.003. 
      Epub 2017 Apr 14.