Abstract
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.
Highlights
The marijuana plant Cannabis sativa contains over 100 components termed cannabinoids [1]
There were no significant differences in demographic characteristics including BMI, cause of death, HbA1c level, blood glucose at admission, and cold ischemia time between non-users and marijuana-users (Table 1)
We report a negative relationship between chronic marijuana use and human islet morphology and function
Summary
The marijuana plant Cannabis sativa contains over 100 components termed cannabinoids [1]. Cannabinoids interact with cannabinoid receptors, including type 1 (CB1R) and type 2 (CB2R), on the cell membrane to regulate several signaling pathways [2] that modulate food intake, increase appetite [3], and regulate lipid and glucose homoeostasis and insulin sensitivity [4]. Marijuana and human islets in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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