PMID- 32769216
OWN - NLM
STAT- MEDLINE
DCOM- 20210615
LR  - 20210615
IS  - 1437-4315 (Electronic)
IS  - 1431-6730 (Linking)
VI  - 401
IP  - 11
DP  - 2020 Oct 25
TI  - Individual and combined effects of GIP and xenin on differentiation, glucose 
      uptake and lipolysis in 3T3-L1 adipocytes.
PG  - 1293-1303
LID - 10.1515/hsz-2020-0195 [doi]
AB  - The incretin hormone glucose-dependent insulinotropic polypeptide (GIP), released 
      postprandially from K-cells, has established actions on adipocytes and lipid 
      metabolism. In addition, xenin, a related peptide hormone also secreted from 
      K-cells after a meal, has postulated effects on energy regulation and lipid 
      turnover. The current study has probed direct individual and combined effects of 
      GIP and xenin on adipocyte function in 3T3-L1 adipocytes, using enzyme-resistant 
      peptide analogues, (d-Ala2)GIP and xenin-25-Gln, and knockdown (KD) of receptors 
      for both peptides. (d-Ala2)GIP stimulated adipocyte differentiation and lipid 
      accumulation in 3T3-L1 adipocytes over 96 h, with xenin-25-Gln evoking similar 
      effects. Combined treatment significantly countered these individual adipogenic 
      effects. Individual receptor KD impaired lipid accumulation and adipocyte 
      differentiation, with combined receptor KD preventing differentiation. 
      (d-Ala2)GIP and xenin-25-Gln increased glycerol release from 3T3-L1 adipocytes, 
      but this lipolytic effect was significantly less apparent with combined 
      treatment. Key adipogenic and lipolytic genes were upregulated by (d-Ala2)GIP or 
      xenin-25-Gln, but not by dual peptide culture. Similarly, both (d-Ala2)GIP and 
      xenin-25-Gln stimulated insulin-induced glucose uptake in 3T3-L1 adipocytes, but 
      this effect was annulled by dual treatment. In conclusion, GIP and xenin possess 
      direct, comparable, lipogenic and lipolytic actions in 3T3-L1 adipocytes. 
      However, effects on lipid metabolism are significantly diminished by combined 
      administration.
FAU - English, Andrew
AU  - English A
AD  - SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern 
      Ireland, UK.
FAU - Craig, Sarah L
AU  - Craig SL
AD  - SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern 
      Ireland, UK.
FAU - Flatt, Peter R
AU  - Flatt PR
AD  - SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern 
      Ireland, UK.
FAU - Irwin, Nigel
AU  - Irwin N
AD  - SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern 
      Ireland, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Biol Chem
JT  - Biological chemistry
JID - 9700112
RN  - 144092-28-4 (xenin 25)
RN  - 39379-15-2 (Neurotensin)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/metabolism
MH  - Animals
MH  - Cell Differentiation
MH  - Gastric Inhibitory Polypeptide/*metabolism
MH  - Glucose/*metabolism
MH  - *Lipolysis
MH  - Mice
MH  - Neurotensin/*metabolism
OTO - NOTNLM
OT  - 3T3-L1 adipocytes
OT  - differentiation
OT  - glucose uptake
OT  - glucose-dependent insulinotropic polypeptide (GIP)
OT  - lipid metabolism
OT  - xenin
EDAT- 2020/08/10 06:00
MHDA- 2021/06/16 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/05/22 00:00 [received]
PHST- 2020/08/04 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - /j/bchm.just-accepted/hsz-2020-0195/hsz-2020-0195.xml [pii]
AID - 10.1515/hsz-2020-0195 [doi]
PST - ppublish
SO  - Biol Chem. 2020 Oct 25;401(11):1293-1303. doi: 10.1515/hsz-2020-0195.