| Title: |
Effects of prolonged exposure to pancreatic glucagon on the function, antigenicity and survival of isolated human islets |
| Authors: |
Del Guerra S.; Lupi R.; Dotta F.; Marselli L.; Lencioni C.; Santangelo C.; Realacci M.; Carmellini M.; Mosca F.; Navalesi R.; Marchetti P. |
| Contributors: |
Del Guerra, S.; Lupi, R.; Dotta, F.; Marselli, L.; Lencioni, C.; Santangelo, C.; Realacci, M.; Carmellini, M.; Mosca, F.; Navalesi, R.; Marchetti, P. |
| Publication Year: |
2000 |
| Collection: |
Università degli Studi di Siena: USiena air |
| Subject Terms: |
Bcl-2; Chemotaxi; Cytokine; Glucagon; Human islet; Insulin release |
| Description: |
BACKGROUND: Certain clinical conditions are associated with inappropriately high levels of circulating glucagon. To date, little information is available about the direct effects of prolonged exposure of human islet cells to pancreatic glucagon. In the present study we evaluated the function, antigenicity and survival of human islets exposed for 24 h to human pancreatic glucagon. METHODS: We prepared human islets of Langerhans by collagenase digestion and density-gradient purification, incubated them for 24 h with 44 or 430 pmol/l pancreatic glucagon at physiological (5.5 mmol/l) glucose level, and evaluated their insulin release function, which was then compared with that obtained from islets kept at high (11.1 mmol/l) glucose concentration. In addition, aliquots of the islets were evaluated to assess their chemotactic properties towards human monocyte-macrophage cells, and their potency to induce cytokine release from human lymphocytes. Finally, survival of the islet cells cultured under varying conditions was evaluated, and an assessment was performed of mRNA expression of Bcl-2 and Bax proteins. RESULTS: The insulin secretion results demonstrated that, compared to the control islets, the islets previously exposed to either 44 or 430 pmol/l glucagon exhibited changes in insulin release in response to glucose, consisting of augmented secretion at low glucose challenge, and no further significant increase at high glucose stimulation, similar to the effects observed with islets pre-cultured with high glucose. These effects were reversible, as documented by the recovery of normal islet sensitivity to glucose after an additional 24-h culture in medium lacking glucagon. Compared to control islets, the culture medium from islets pre-cultured with high glucagon or high glucose showed an increased chemotactic potency towards human monocyte-macrophage cells. In addition, human lymphocytes released a greater amount of tumour necrosis factor alpha when co-cultured with the islets pre-exposed to high glucagon or high ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/10934457; info:eu-repo/semantics/altIdentifier/wos/WOS:000088682400008; volume:16; issue:4; firstpage:281; lastpage:286; numberofpages:6; journal:DIABETES/METABOLISM RESEARCH AND REVIEWS; http://hdl.handle.net/11365/42061 |
| DOI: |
10.1002/1520-7560(2000)9999:99993.0.CO;2-Q?src=getftr |
| Availability: |
http://hdl.handle.net/11365/42061; https://onlinelibrary.wiley.com/doi/epdf/10.1002/1520-7560(2000)9999:99993.0.CO;2-Q?src=getftr |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.7ECB946F |
| Database: |
BASE |