Beta cell death in hyperglycaemic Psammomys obesus is not cytokine-mediated.
OBJECTIVE
It has recently been proposed that IL-1beta may be responsible for beta cell death in type 2 diabetes mellitus. Major support for this assumption was derived from experiments in the gerbil Psammomys obesus (sand rat), a model for nutritionally induced non-insulin-dependent type 2 diabetes. Using gerbil-specific primers for the analysis of gene expression, we investigated the validity of this hypothesis.


METHODS
Gene expression was analysed by real-time RT-PCR of isolated and laser-microdissected islets and by in situ RT-PCR, both in beta cells and in immune cells, as well as in lymph nodes and spleen.


RESULTS
We were unable to detect Il-1beta and the IL-1beta-inducible enzyme inducible nitric oxide synthase (iNos) by in situ RT-PCR, either in the pancreatic beta cells, or in the small number of non-activated immune cells of healthy and diabetic Psammomys obesus after 1 and 3 weeks on a high-energy diet. Very low levels of Il-1beta and iNos mRNA were detectable in collagenase-isolated and laser-microdissected islets of normoglycaemic gerbils by real-time RT-PCR without any increase of these mRNAs in islets from diabetic animals. These results were confirmed by electron microscopy with immunogold staining for IL-1beta and insulin.


CONCLUSIONS
The diabetic syndrome induced in Psammomys obesus by high-energy diet is a classical type 2 diabetes model, which does not show any evidence of an involvement of the proinflammatory cytokine IL-1beta or of activated immune cells in its pathogenesis. This is clearly at variance with the situation in type 1 diabetes.
Jörns
A
A
Centre of Anatomy and Institute of Clinical Biochemistry, Hannover Medical School, 30625 Hannover, Germany. joerns.anne@mh-hannover.de
Rath
K J
KJ
Bock
O
O
Lenzen
S
S
D000818:Animals; D016923:Cell Death; D016207:Cytokines / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D004195:Disease Models, Animal; D005849:Gerbillinae; D006943:Hyperglycemia / Q000473:pathology*; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II