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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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0258434
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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
collection DOAJ
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.
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spelling doaj.art-b70039e55f674174bd375585cc3aecb32023-06-20T05:31:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011610e025843410.1371/journal.pone.0258434Chronic marijuana usage by human pancreas donors is associated with impaired islet function.Meirigeng QiJohn S KaddisKuan-Tsen ChenJeffrey RawsonKeiko OmoriZhen Bouman ChenSangeeta DhawanJeffrey S IsenbergFouad KandeelBart O RoepIsmail H Al-AbdullahWe 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.https://doi.org/10.1371/journal.pone.0258434
spellingShingle 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.
PLoS ONE
title 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_short 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
url https://doi.org/10.1371/journal.pone.0258434
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