Chronic Marijuana Use May Impair Donor Islet Cells

By Marilynn Larkin

November 23, 2021

NEW YORK (Reuters Health) - Donor islet cells from chronic marijuana users were not as effective in reversing diabetes in vitro and in mice as islet cells from non-marijuana users, suggesting that transplanted cells from users may not function optimally, researchers say.

Chronic marijuana use was defined as four times weekly for more than three years.

"We conducted this study because the number of donors that are using marijuana has been increasing," Dr. Ismail Al-Abdullah of City of Hope in Duarte, California, told Reuters Health by email. "The isolated islets from the pancreata of marijuana users appeared to be of lower quality, displayed reduced insulin secretion and appeared enlarged. Therefore, we decided to further investigate the impact of heavy marijuana use."

As reported in PLOS One, Dr. Al-Abdullah and colleagues analyzed pancreata received at City of Hope from 2006-2016 from 206 deceased donors. Donors were divided into two groups based on the medical and social histories documented in the donor charts provided by the organ procurement organizations at the time of placing the pancreas offer.

The marijuana group included 26 donors. Overall, donors' mean age at death was 40 and about 31% were women; about 65% were white; 28%, Hispanic/Latino; and 10%, African American.

Matched donor subsets were identified in both groups to limit bias effect estimates from the covariates of age, sex, and ethnicity.

Islets from marijuana users showed reduced insulin secretion compared to islets from non-users when stimulated with high glucose (area under the curve, 3.41) and high glucose plus KCl (AUC, 4.48).

When human islets from chronic marijuana users were transplanted into diabetic mice, the mean diabetes reversal rate was 35% with islets from users versus 77% in animals receiving islets from non-users.

Immunofluorescent staining showed cannabinoid receptor type 1 (CB1R) was colocalized with insulin and enhanced significantly in beta cells from users versus non-users (CB1R intensity/islet area, 14.95 +/- 2.71 vs. 3.23).

By contrast, CB1R expression was not co-localized with glucagon or somatostatin.

In addition, isolated islets from chronic users appeared hypertrophic, as Dr. Al-Abdullah noted.

Dr. Al Abdullah said, "Our study makes a case for thorough assessment of donor lifestyle activities, including marijuana use, when clinicians are evaluating human islets for transplantation or research."

"We are currently conducting a mechanistic study regarding the impact of cannabinoid on human islets," he added. "We would like to investigate the effect of other widely-used drugs so that we will be able to discover the potentially detrimental effect of these drugs on islets and other pancreatic tissues."

Dr. Zoe Stewart Lewis, surgical director of the kidney and pancreas transplant programs and director of quality at the NYU Langone Transplant Institute, commented on the study in an email to Reuters Health. "This practice (taking lifestyle into consideration) is already standard of care for organ donors," she said. "The medical and psychosocial history of all organ donors is carefully screened during evaluation to identify factors that could impact either organ function or risk to the recipient for infection transmission."

"While this is an interesting area of research that warrants further study, I think it is very premature to conclude that pancreas transplant donor organ utilization practices should be modified in response to the current report," she noted. "There are several key limitations, including the small sample size and the fact that this study looks at the function of isolated islets cells versus the function of a whole organ."

"Additionally," she said, "the islet cells in the study were recovered from donors who fall outside of the accepted donor criteria for whole organ pancreas transplant for both age >40 years and donors that were either overweight or had class I obesity."

"Further studies are needed in pancreas transplant recipients to determine if the long-term use of marijuana impacts allograft function," she said.

SOURCE: https://bit.ly/3l2uT7h PLOS One, online October 27, 2021.

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