Open AccessChronic marijuana usage by human pancreas donors is associated with impaired islet function
Author(s) -
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
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0258434
Subject(s) - islet , medicine , endocrinology , diabetes mellitus , glucagon , pancreas , insulin , stimulation , type 1 diabetes , transplantation
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.