Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.
OBJECTIVE
Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected.


METHODS
Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy.


RESULTS
Culture at 15 mmol/l glucose increased islet glucagon content by approximately 50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by approximately 50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in <10% of non-beta cells but in >80% of the beta cells.


CONCLUSIONS
Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.
Collins
S C
SC
OCDEM, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. stephan.collins@drl.ox.ac.uk
Salehi
A
A
Eliasson
L
L
Olofsson
C S
CS
Rorsman
P
P
D000818:Animals; D002478:Cells, Cultured; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology*; D019308:Palmitic Acid / Q000494:pharmacology*; D010879:Piperazines; D013004:Somatostatin / Q000378:metabolism*; D014230:Triazoles
D010879:Piperazines; D014230:Triazoles; D019301:Oleic Acid; D019308:Palmitic Acid; D013004:Somatostatin; C051752:nefazodone; D005934:Glucagon; D005947:Glucose