Endothelial cell signalling supports pancreatic beta cell function in the rat.
OBJECTIVE
The proximity of endothelial cells and beta cells in islets by necessity means that they are exposed to each other's products. Whereas islet endothelial cells require signals from beta cells to function properly, endothelin-1, thrombospondin-1 and laminins, among others, have been identified as endothelial-derived molecules, although their full effects on beta cells have not been explored. We tested the hypothesis that islet endothelial-derived products affect beta cell function.


METHODS
Endothelial cells from rat islets were proliferated and purified. Endothelium-conditioned culture medium (ECCM) was obtained by maintaining the endothelial cells in culture medium. Islet function was evaluated following exposure of cultured islets to standard culture medium or ECCM. Changes in mRNA levels for key beta cell metabolic enzymes were also measured in islets after ECCM exposure.


RESULTS
Glucose-stimulated insulin release and islet insulin content were markedly enhanced by exposure to ECCM. This was at least partly explained by improved mitochondrial function, as assessed by glucose oxidation and an upregulation of the mitochondrial gene for glycerol-3-phosphate dehydrogenase (mGpdh [also known as Gpd2]), combined with upregulation of the rate-limiting enzyme in the glycolysis, glucokinase, in the islets. The intracellular degradation of insulin was also decreased in the islets. Islet endothelial cells produced laminins, and the positive effects of islet endothelial cells were prevented by addition of a neutralising antibody to the beta1-chain of laminin. Addition of exogenous laminin stimulated islet function.


CONCLUSIONS
This study provides proof of principle that endothelial cells can affect the function of beta cells in their vicinity and that this is at least partially mediated by laminins.
Johansson
A
A
Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden. asa.johansson@mcb.uu.se
Lau
J
J
Sandberg
M
M
Borg
L A H
LA
Magnusson
P U
PU
Carlsson
P-O
PO
D000818:Animals; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006019:Glycolysis / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D007515:Islets of Langerhans / Q000098:blood supply; D007783:Lactones / Q000494:pharmacology; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D015398:Signal Transduction / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology
D017077:Culture Media, Conditioned; D052246:Cyclooxygenase 2 Inhibitors; D007328:Insulin; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D005947:Glucose