Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1864, Issue 6, Pages 2169-2182Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2018.03.022
Keywords
Caveolin-2; Alternative translation initiation; Insulin receptor; Protein tyrosine phosphatase 1B; Lysosomal degradation; Insulin resistance
Funding
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2011-0014898]
- Ministry of Education (ME) [NRF-2015R1D1A3A01016537, NRF-2015R1D1A4A01017437, NRF-2018R1C1B6006816, NRF-2015R1A6A3A01016424]
- National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea [1631090]
- Next-Generation BioGreen 21 Program from the Rural Development Administration of Korea (SSAC) [PJ01137901]
- Development Fund Foundation, Gyeongsang National University
- Global Ph.D. Fellowship Program [NRF-2013H1A2A1034489]
- BK21 Plus Program
- Korea Health Promotion Institute [1631090] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2018R1D1A1B07045995] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2 beta isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2 beta-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2 beta is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available