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...

Full description

Bibliographic Details
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://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550598/?tool=EBI
_version_ 1818717200590045184
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.
first_indexed 2024-12-17T19:31:22Z
format Article
id doaj.art-4b7a770ce1a7403aa1ed7fa083396837
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-17T19:31:22Z
publishDate 2021-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-4b7a770ce1a7403aa1ed7fa0833968372022-12-21T21:35:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-011610Chronic marijuana usage by human pancreas donors is associated with impaired islet functionMeirigeng 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550598/?tool=EBI
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://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550598/?tool=EBI
work_keys_str_mv AT meirigengqi chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT johnskaddis chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT kuantsenchen chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT jeffreyrawson chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT keikoomori chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT zhenboumanchen chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT sangeetadhawan chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT jeffreysisenberg chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT fouadkandeel chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT bartoroep chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction
AT ismailhalabdullah chronicmarijuanausagebyhumanpancreasdonorsisassociatedwithimpairedisletfunction