Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon
(2008) In Diabetologia 51(9). p.1689-1693- 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 similar to 50% relative to that observed following culture at 4.5 mmol/l... (More)
- 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 similar to 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 similar to 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1253466
- author
- Collins, S. C. ; Salehi, S Albert LU ; Eliasson, Lena LU ; Olofsson, C. S. and Rorsman, P.
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- palmitate, oleate, NEFA, glucolipotoxicity, diabetes, glucagon, somatostatin
- in
- Diabetologia
- volume
- 51
- issue
- 9
- pages
- 1689 - 1693
- publisher
- Springer
- external identifiers
-
- wos:000258236200019
- scopus:49249115161
- pmid:18622593
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-008-1082-0
- language
- English
- LU publication?
- yes
- id
- 5f55f4fd-5aaa-41c3-9157-1e4b55bed481 (old id 1253466)
- date added to LUP
- 2016-04-01 12:24:04
- date last changed
- 2022-03-29 00:24:23
@article{5f55f4fd-5aaa-41c3-9157-1e4b55bed481, 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 similar to 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 similar to 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.}}, author = {{Collins, S. C. and Salehi, S Albert and Eliasson, Lena and Olofsson, C. S. and Rorsman, P.}}, issn = {{1432-0428}}, keywords = {{palmitate; oleate; NEFA; glucolipotoxicity; diabetes; glucagon; somatostatin}}, language = {{eng}}, number = {{9}}, pages = {{1689--1693}}, publisher = {{Springer}}, series = {{Diabetologia}}, title = {{Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon}}, url = {{http://dx.doi.org/10.1007/s00125-008-1082-0}}, doi = {{10.1007/s00125-008-1082-0}}, volume = {{51}}, year = {{2008}}, }