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Diabetologia. 2008 Sep;51(9):1689-93. doi: 10.1007/s00125-008-1082-0. Epub 2008 Jul 12.

Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.

Author information

1
OCDEM, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. stephan.collins@drl.ox.ac.uk

Abstract

AIMS/HYPOTHESIS:

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/INTERPRETATION:

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.

PMID:
18622593
PMCID:
PMC2516194
DOI:
10.1007/s00125-008-1082-0
[Indexed for MEDLINE]
Free PMC Article

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