Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing.
OBJECTIVE
Under conditions of insulin resistance and type 2 diabetes, fat cells are subjected to increased levels of insulin, which may have a major impact on the secretion of adipokines.


METHODS
Using transcriptomics and proteomics, we investigated how insulin affects the transcription and protein secretion profile of mature 3T3-L1 adipocytes.


RESULTS
We found that insulin has a significant impact on protein secretion of 3T3-L1 adipocytes. However, transcription is not the major regulation point for these secreted proteins. For extracellular matrix components, our data suggest that the mRNA level of processing enzymes, but not of target proteins, is the regulating point at which insulin stimulates secretion and function of the relevant proteins. Among these enzymes, we report a novel finding, namely that sulfatase 2 gene is regulated by insulin, which may induce a functional change in cultured adipocytes.


CONCLUSIONS
We propose that enhancement of protein processing and secretion rather than transcription of the secreted protein genes is part of the strategic role of insulin in the induction of cellular responses.
Wang
P
P
Functional Genomics Group, Research Institute NUTRIM, Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
Keijer
J
J
Bunschoten
A
A
Bouwman
F
F
Renes
J
J
Mariman
E
E
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D004798:Enzymes / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects*
D004798:Enzymes; D007328:Insulin; D011506:Proteins; D012333:RNA, Messenger; D005947:Glucose