A novel hormone-sensitive lipase isoform expressed in pancreatic beta -cells.
(2004) In Journal of Biological Chemistry 279(5). p.3828-3836- Abstract
- Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSLadi (84 kDa in rat) and HSLtes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5'-exon encoding the additional amino acids in HSLtes. HSL of various tissues, among these the islet of Langerhans, is larger than HSLadi, but not as large as HSLtes, indicating that there may be other 5'-coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in -cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and... (More)
- Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSLadi (84 kDa in rat) and HSLtes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5'-exon encoding the additional amino acids in HSLtes. HSL of various tissues, among these the islet of Langerhans, is larger than HSLadi, but not as large as HSLtes, indicating that there may be other 5'-coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in -cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and thereby introducing an upstream start codon. The additional 5'-base pairs encode a 43-amino acid peptide, which is highly positively charged. Conglomerates of HSL molecules are in close association with the secretory granules of the -cell, as determined by immunoelectron microscopy with antibodies targeting two separate regions of HSL. We have also determined that the human genomic sequence upstream of exon A has promoter activity in INS-1 cells as well as glucose sensing capability, mediating an increase in expression at high glucose concentration. The minimal promoter is present within 170 bp from the transcriptional start site and maximal glucose responsiveness is conferred by sequence within 850 bp from the transcriptional start site. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/118215
- author
- Lindvall, Håkan LU ; Nevsten, Pernilla LU ; Ström, Kristoffer LU ; Wallenberg, Reine LU ; Sundler, Frank LU ; Langin, Dominique ; Sörhede Winzell, Maria LU and Holm, Cecilia LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 5
- pages
- 3828 - 3836
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000188379600085
- pmid:14576146
- scopus:0942265525
- pmid:14576146
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M311365200
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Polymer and Materials Chemistry (LTH) (011001041), Department of Experimental Medical Science (013210000), Molecular Endocrinology (013212018), Medicine (Lund) (013230025)
- id
- 2c0de301-c201-4ad7-806f-739e78d24011 (old id 118215)
- date added to LUP
- 2016-04-01 12:30:20
- date last changed
- 2024-01-08 22:48:07
@article{2c0de301-c201-4ad7-806f-739e78d24011,
abstract = {{Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many cell types. Two isoforms of HSL are known to date, namely HSLadi (84 kDa in rat) and HSLtes (130 kDa in rat). These are encoded by the same gene, with exons 1-9 encoding the parts that are common to both and an additional 5'-exon encoding the additional amino acids in HSLtes. HSL of various tissues, among these the islet of Langerhans, is larger than HSLadi, but not as large as HSLtes, indicating that there may be other 5'-coding exons. Here we describe the molecular basis for a novel 89-kDa HSL isoform that is expressed in -cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by exons 1-9 and exon A, which is spliced to exon 1 and thereby introducing an upstream start codon. The additional 5'-base pairs encode a 43-amino acid peptide, which is highly positively charged. Conglomerates of HSL molecules are in close association with the secretory granules of the -cell, as determined by immunoelectron microscopy with antibodies targeting two separate regions of HSL. We have also determined that the human genomic sequence upstream of exon A has promoter activity in INS-1 cells as well as glucose sensing capability, mediating an increase in expression at high glucose concentration. The minimal promoter is present within 170 bp from the transcriptional start site and maximal glucose responsiveness is conferred by sequence within 850 bp from the transcriptional start site.}},
author = {{Lindvall, Håkan and Nevsten, Pernilla and Ström, Kristoffer and Wallenberg, Reine and Sundler, Frank and Langin, Dominique and Sörhede Winzell, Maria and Holm, Cecilia}},
issn = {{1083-351X}},
language = {{eng}},
number = {{5}},
pages = {{3828--3836}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{A novel hormone-sensitive lipase isoform expressed in pancreatic beta -cells.}},
url = {{http://dx.doi.org/10.1074/jbc.M311365200}},
doi = {{10.1074/jbc.M311365200}},
volume = {{279}},
year = {{2004}},
}