Insulin upregulates betatrophin expression via PI3K/Akt pathway

Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:7

Enthalten in:

Scientific reports - 7(2017), 1 vom: 17. Juli, Seite 5594

Sprache:

Englisch

Beteiligte Personen:

Lu, Puhan [VerfasserIn]
Chen, Xi [VerfasserIn]
Zhang, Zeqing [VerfasserIn]
Zhang, Jianhua [VerfasserIn]
Yang, Yan [VerfasserIn]
Liu, Zhelong [VerfasserIn]
Xie, Junhui [VerfasserIn]
Shao, Shiying [VerfasserIn]
Zhou, Xinrong [VerfasserIn]
Hu, Shuhong [VerfasserIn]
He, Wentao [VerfasserIn]
Zhao, Jiajun [VerfasserIn]
Yu, Xuefeng [VerfasserIn]

Links:

Volltext

Themen:

9100L32L2N
ANGPTL8 protein, human
ANGPTL8 protein, mouse
Angiopoietin-Like Protein 8
Angiopoietin-like Proteins
EC 2.7.11.1
Glucose
Hypoglycemic Agents
IY9XDZ35W2
Insulin
Journal Article
Metformin
Peptide Hormones
Proto-Oncogene Proteins c-akt
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 15.02.2019

Date Revised 09.04.2022

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-017-06052-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM273927949