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PMID: 18664535 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation.

The Journal of clinical endocrinology and metabolism ·Vol. 93 ·No. 10 ·2008-10-00 ·Pages 4065-74

Böni-Schnetzler M, Thorne J, Parnaud G, Marselli L, Ehses JA, Kerr-Conte J, Pattou F, Halban PA, Weir GC, Donath MY

Abstract

Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1beta contributes to glucotoxicity. The objective was to investigate IL-1beta mRNA expression in near-pure beta-cells of patients with type 2 diabetes (T2DM) and study the regulation of IL-1beta by glucose in isolated human islets. Laser capture microdissection was performed to isolate beta-cells from pancreas sections of 10 type 2 diabetic donors and nine controls, and IL-1beta mRNA expression was analyzed using gene arrays and PCR. Cultured human islets and fluorescence-activated cell sorter-purified human beta-cells were used to study the regulation of IL-1beta expression by glucose and IL-1beta. Gene array analysis of RNA from beta-cells of individuals with T2DM revealed increased expression of IL-1beta mRNA. Real-time PCR confirmed increased IL-1beta expression in six of 10 T2DM samples, with minimal or no expression in nine control samples. In cultured human islets, IL-1beta mRNA and protein expression was induced by high glucose and IL-1beta autostimulation and decreased by the IL-1 receptor antagonist IL-1Ra. The glucose response was negatively correlated with basal IL-1beta expression levels. Autostimulation was transient and nuclear factor-kappaB dependent. Glucose-induced IL-1beta was biologically active and stimulated IL-8 release. Low picogram per milliliter concentrations of IL-1beta up-regulated inflammatory factors IL-8 and IL-6. Evidence that IL-1beta mRNA expression is up-regulated in beta-cells of patients with T2DM is presented, and glucose-promoted IL-1beta autostimulation may be a possible contributor.

MeSH Terms
Autocrine Communication/drug effects,genetics,physiology Cells, Cultured Diabetes Mellitus, Type 2/genetics,metabolism Gene Expression Profiling Glucose/pharmacology Humans Insulin-Secreting Cells/metabolism Interleukin-1beta/genetics,metabolism,pharmacology Interleukin-6/genetics Interleukin-8/genetics Islets of Langerhans/drug effects,metabolism NF-kappa B/physiology Oligonucleotide Array Sequence Analysis RNA, Messenger/metabolism Up-Regulation/drug effects
Chemicals
Interleukin-1beta Interleukin-6 Interleukin-8 NF-kappa B RNA, Messenger Glucose
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Böni-Schnetzler Marianne
Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. [email protected]
Thorne Jeffrey
Parnaud Géraldine
Marselli Lorella
Ehses Jan A
Kerr-Conte Julie
Pattou Francois
Halban Philippe A
Weir Gordon C
Donath Marc Y
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Article Info
Journal
The Journal of clinical endocrinology and metabolism
Abbr.
J Clin Endocrinol Metab
ISSN
0021-972X
DOI
10.1210/jc.2008-0396
Email
[email protected]
Published
2008-10-00
Epub
2008-00-29
Pages
4065-74
Language
English
Region
United States
NLM ID
0375362
PMCID
PMC2579638
Subset
IM
Grants
NCRR NIH HHS · U42 RR016606 · United States
NIDDK NIH HHS · U19DK6125 · United States
NCRR NIH HHS · U4Z RR 16606 · United States
External Links
PubMed source DOI: 10.1210/jc.2008-0396 PMC Full Text View journal details
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