Chronic marijuana usage by human pancreas donors is associated with impaired islet function.
We investigated the effect of chronic marijuana use, defined as 4 times weekly for more than 3 years, on human pancreatic islets. Pancreata from deceased donors who chronically used marijuana were compared to those from age, sex and ethnicity matched non-users. The islets from marijuana-users displa...
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oai:doaj.org-article:b70039e55f674174bd375585cc3aecb32021-12-02T20:16:33ZChronic marijuana usage by human pancreas donors is associated with impaired islet function.1932-620310.1371/journal.pone.0258434https://doaj.org/article/b70039e55f674174bd375585cc3aecb32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258434https://doaj.org/toc/1932-6203We investigated the effect of chronic marijuana use, defined as 4 times weekly for more than 3 years, on human pancreatic islets. Pancreata from deceased donors who chronically used marijuana were compared to those from age, sex and ethnicity matched non-users. The islets from marijuana-users displayed reduced insulin secretion as compared to islets from non-users upon stimulation with high glucose (AUC, 3.41 ± 0.62 versus 5.14 ±0.47, p<0.05) and high glucose plus KCl (AUC, 4.48 ± 0.41 versus 7.69 ± 0.58, p<0.001). When human islets from chronic marijuana-users were transplanted into diabetic mice, the mean reversal rate of diabetes was 35% versus 77% in animals receiving islets from non-users (p<0.01). Immunofluorescent staining for cannabinoid receptor type 1 (CB1R) was shown to be colocalized with insulin and enhanced significantly in beta cells from marijuana-users vs. non-users (CB1R intensity/islet area, 14.95 ± 2.71 vs. 3.23 ± 0.87, p<0.001). In contrast, CB1R expression was not co-localized with glucagon or somatostatin. Furthermore, isolated islets from chronic marijuana-users appeared hypertrophic. In conclusion, excessive marijuana use affects islet endocrine phenotype and function in vitro and in vivo. Given the increasing use of marijuana, our results underline the importance of including lifestyle when evaluating human islets for transplantation or research.Meirigeng QiJohn S KaddisKuan-Tsen ChenJeffrey RawsonKeiko OmoriZhen Bouman ChenSangeeta DhawanJeffrey S IsenbergFouad KandeelBart O RoepIsmail H Al-AbdullahPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258434 (2021) |
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Medicine R Science Q Meirigeng Qi John S Kaddis Kuan-Tsen Chen Jeffrey Rawson Keiko Omori Zhen Bouman Chen Sangeeta Dhawan Jeffrey S Isenberg Fouad Kandeel Bart O Roep Ismail H Al-Abdullah Chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
description |
We investigated the effect of chronic marijuana use, defined as 4 times weekly for more than 3 years, on human pancreatic islets. Pancreata from deceased donors who chronically used marijuana were compared to those from age, sex and ethnicity matched non-users. The islets from marijuana-users displayed reduced insulin secretion as compared to islets from non-users upon stimulation with high glucose (AUC, 3.41 ± 0.62 versus 5.14 ±0.47, p<0.05) and high glucose plus KCl (AUC, 4.48 ± 0.41 versus 7.69 ± 0.58, p<0.001). When human islets from chronic marijuana-users were transplanted into diabetic mice, the mean reversal rate of diabetes was 35% versus 77% in animals receiving islets from non-users (p<0.01). Immunofluorescent staining for cannabinoid receptor type 1 (CB1R) was shown to be colocalized with insulin and enhanced significantly in beta cells from marijuana-users vs. non-users (CB1R intensity/islet area, 14.95 ± 2.71 vs. 3.23 ± 0.87, p<0.001). In contrast, CB1R expression was not co-localized with glucagon or somatostatin. Furthermore, isolated islets from chronic marijuana-users appeared hypertrophic. In conclusion, excessive marijuana use affects islet endocrine phenotype and function in vitro and in vivo. Given the increasing use of marijuana, our results underline the importance of including lifestyle when evaluating human islets for transplantation or research. |
format |
article |
author |
Meirigeng Qi John S Kaddis Kuan-Tsen Chen Jeffrey Rawson Keiko Omori Zhen Bouman Chen Sangeeta Dhawan Jeffrey S Isenberg Fouad Kandeel Bart O Roep Ismail H Al-Abdullah |
author_facet |
Meirigeng Qi John S Kaddis Kuan-Tsen Chen Jeffrey Rawson Keiko Omori Zhen Bouman Chen Sangeeta Dhawan Jeffrey S Isenberg Fouad Kandeel Bart O Roep Ismail H Al-Abdullah |
author_sort |
Meirigeng Qi |
title |
Chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
title_short |
Chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
title_full |
Chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
title_fullStr |
Chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
title_full_unstemmed |
Chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
title_sort |
chronic marijuana usage by human pancreas donors is associated with impaired islet function. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/b70039e55f674174bd375585cc3aecb3 |
work_keys_str_mv |
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