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Regulation of insulin and glucagon secretion from rat pancreatic islets in vitro by somatostatin analogues
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Klinisk kemi)
(Biomeasure, Inc./Beaufour-IPSEN Group, Milford, PA, USA)
(Biomeasure, Inc./Beaufour-IPSEN Group, Milford, PA, USA)
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2007 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 138, no 1, 1-9 p.Article in journal (Refereed) Published
Abstract [en]

Somatostatin is an inhibitor of hormone secretion through specific receptors (sst1-5). The aim of this study was to investigate the putative regulatory role of somatostatin analogues on the secretion of insulin and glucagon by rat pancreatic islets. After 48 h exposure only the non-selective agonists (somatostatin, octreotide and SOM-230) inhibited insulin accumulation. The inhibition of insulin secretion was accompanied by increased islet insulin contents. None of the analogues showed a consistent effect on the glucagon accumulation in the medium after 48 h. Since we observed a difference in the regulatory effect between the non-selective and selective analogues, combinations of selective analogues were studied. Combination of sst2 + sst5 agonists inhibited the medium insulin accumulation, while combination of sst1 + sst2 analogues caused a decrease in glucagon accumulation. After removal of somatostatin a rebound effect with increased insulin secretion were observed. This effect was reversed after 6 h. For SOM-230 insulin secretion continued to be suppressed even after the analogue was removed and returned to control values after 3 h. As for glucagon secretion there was an initial decline after culture with octreotide, while the other substances failed to induce any changes. In summary, non-selective somatostatin analogues or combinations of receptor selective analogues may cause inhibition of hormone secretion from rat pancreatic islets. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively may exert this effects. Thus, our data suggest that more than one sst must be involved to down-regulate islet glucagon and insulin secretion.

Place, publisher, year, edition, pages
2007. Vol. 138, no 1, 1-9 p.
Keyword [en]
Glucagon secretion, Insulin secretion, Pancreatic islets, Somatostatin analogues, Somatostatin receptors
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93890DOI: 10.1016/j.regpep.2006.07.006ISI: 000243772600001PubMedID: 16935361OAI: oai:DiVA.org:uu-93890DiVA: diva2:167521
Available from: 2006-01-13 Created: 2006-01-13 Last updated: 2011-02-16Bibliographically approved
In thesis
1. Somatostatin Receptor Expression and Biological Functions in Endocrine Pancreatic Cells
Open this publication in new window or tab >>Somatostatin Receptor Expression and Biological Functions in Endocrine Pancreatic Cells
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 diabetes is resulting from the selective destruction of insulin-producing beta-cells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5).

All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species.

The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction.

Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via co-stimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect.

In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of these cells during the autoimmune attack.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 45 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 94
Cell biology, somatostatin, somatostatin receptors, somatostatin analogues, NOD mouse, type 1 diabetes, pancreatic islets, BON-1 cells, Cellbiologi
National Category
Cell Biology
urn:nbn:se:uu:diva-6249 (URN)91-554-6428-9 (ISBN)
Public defence
2006-02-03, B21, Biomedicinskt centrum, Husargatan 3, Uppsala, 09:15
Available from: 2006-01-13 Created: 2006-01-13Bibliographically approved

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