PMID- 28260721
OWN - NLM
STAT- MEDLINE
DCOM- 20180302
LR  - 20180302
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 40
IP  - 6
DP  - 2017 Jun 1
TI  - The Characteristics of Hepatic Gsalpha-cAMP Axis in HSHF Diet-Fed Obese Insulin 
      Resistance Rats and Genetic Diabetic Mice.
PG  - 774-781
LID - 10.1248/bpb.b16-00749 [doi]
AB  - Stimulatory G protein alpha-subunit (Gsalpha) mediated cAMP signal is required for 
      elevated hepatic glucose production (HGP) in diabetic patients. However, it 
      remains obscure of the exact characteristics of hepatic Gsalpha-cAMP signal axis 
      (including Gsalpha, glucagon receptor, beta(2)-adrenergic receptor, cAMP, 
      phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in insulin 
      resistance (IR) and type 2 diabetes mellitus (T2DM). In current study, we 
      investigated the changing characteristics of hepatic Gsalpha-cAMP signal axis and 
      blood glucose in high-sugar-high-fat (HSHF)-diet-induced IR Wistar rats and db/db 
      diabetic mice. As expected, the HSHF-diet rats were characterized by 
      hyperinsulinemia, hyperglycemia and impaired glucose tolerance. According to a 
      threshold (1.7) of homeostasis model assessment ratio (HOMA-R), the process of IR 
      in HSHF-diet rats could be divided into slight and high IR stages, with the 
      week-23 as the cut-off point. In early slight IR stage, key molecules expressions 
      of hepatic Gsalpha-cAMP signal axis in HSHF-diet rats were up-regulated with 
      significantly elevated fasting blood glucose (FBG) from 18 to 23 weeks. 
      Unexpectedly, in high IR stage, hepatic Gsalpha-cAMP signal axis was recovered 
      comparatively to that of normal chow-diet rats, and no significant differences in 
      FBG levels were found. However, in diabetic db/db mice, up-regulation of hepatic 
      Gsalpha-cAMP signal axis was responsible for its severely increased fasting 
      hyperglycaemia. Our data revealed a positive correlation between hepatic Gsalpha-cAMP 
      signal axis and FBG in slight IR stage of HSHF-diet rats and diabetic db/db mice. 
      The current finding thus suggested hepatic Gsalpha-cAMP signal axis plays a central 
      role in regulating of FBG during the developing and development of T2DM.
FAU - Xue, Nina
AU  - Xue N
AD  - Beijing Institute of Pharmacology and Toxicology.
AD  - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College.
FAU - Wei, Chen
AU  - Wei C
AD  - Beijing Institute of Pharmacology and Toxicology.
FAU - Zhang, Lihong
AU  - Zhang L
AD  - Beijing Institute of Pharmacology and Toxicology.
FAU - Liu, Hongying
AU  - Liu H
AD  - Beijing Institute of Pharmacology and Toxicology.
FAU - Wang, Xiaojuan
AU  - Wang X
AD  - Department of Pharmacology, School of Stomatology, The Fourth Military Medical 
      University.
FAU - Wang, Lili
AU  - Wang L
AD  - Beijing Institute of Pharmacology and Toxicology.
LA  - eng
PT  - Journal Article
DEP - 20170304
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Blood Glucose)
RN  - 0 (Dietary Sugars)
RN  - 0 (GTP-Binding Protein alpha Subunits)
RN  - 0 (Insulin)
RN  - 9007-92-5 (Glucagon)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Cyclic AMP/*metabolism
MH  - Diabetes Mellitus/blood/*metabolism
MH  - Diet, High-Fat
MH  - Dietary Sugars
MH  - Disease Models, Animal
MH  - GTP-Binding Protein alpha Subunits/*metabolism
MH  - Glucagon/blood
MH  - Insulin/blood
MH  - *Insulin Resistance
MH  - Liver/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Obesity/blood/*metabolism
MH  - Rats, Wistar
OTO - NOTNLM
OT  - fasting blood glucose
OT  - hepatic glucose production
OT  - insulin resistance
OT  - stimulatory Galpha signal axis
OT  - type 2 diabetes mellitus
EDAT- 2017/03/07 06:00
MHDA- 2018/03/03 06:00
CRDT- 2017/03/07 06:00
PHST- 2017/03/07 06:00 [pubmed]
PHST- 2018/03/03 06:00 [medline]
PHST- 2017/03/07 06:00 [entrez]
AID - 10.1248/bpb.b16-00749 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2017 Jun 1;40(6):774-781. doi: 10.1248/bpb.b16-00749. Epub 2017 
      Mar 4.