Endocannabinoids Trigger Inflammation that Leads to Diabetes
Researchers at the National Institutes of Health have clarified in rodent and test tube experiments the role that inflammation plays in type 2 diabetes, and revealed a possible molecular target for treating the disease. The researchers say some natural messenger chemicals in the body are involved in an inflammatory chain that can kill cells in the pancreas, which produces insulin.
A report of the finding appears online in Nature Medicine.
“This study is a significant milestone in an ongoing exploration of the endocannabinoid system’s role in the metabolic complications of obesity,” says Kenneth R. Warren, PhD, acting director of NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA), which led the study.
Endocannabinoids are natural messengers in the body that help regulate many biological functions. They are chemically similar to the active compound in marijuana. Recent studies have tied endocannabinoids to the metabolic problems that lead to diabetes. Researchers also have recognised that inflammation appears to play an important role in the pathology of diabetes.
“The identities of the molecular and cellular actors in the inflammatory processes that underlie type 2 diabetes have remained elusive,” explains senior author and NIAAA scientific director George Kunos, MD, PhD. “Our study connects endocannabinoids to an inflammatory cascade leading to the loss of beta cells in the pancreas, which is a hallmark of type 2 diabetes.”
Working with a strain of genetically obese rats that serve as a model for human type 2 diabetes, Dr Kunos and his colleagues used a combination of pharmacological and genetic tools to show that endocannabinoids trigger receptors on macrophages in the pancreas. Macrophages are immune system cells, present in all tissues that rid the body of cellular debris and pathogens.
“Like various other peripheral tissues, such as the liver, skeletal muscles, pancreas, and fatty tissue, macrophages have receptors for endocannabinoids,” explains Dr Kunos.
The researchers demonstrated that endocannabinoid activation of macrophages in the pancreas leads to activation of a protein complex within macrophages called the Nlrp3 inflammasome. The inflammasome, in turn, releases molecules that cause the death of pancreatic beta cells and the progression of type 2 diabetes in the rats.
“When we treated the rats with compounds that deplete macrophages or block all peripheral cannabinoid receptors, inflammasome activation and type 2 diabetes progression was slowed,” noted Dr Kunos.
In test tube experiments, the researchers showed that macrophages from humans and mice produced the same inflammasome response when they were incubated with endocannabinoids. However, mouse macrophages that were genetically altered to lack cannabinoid receptors or inflammasomes generated no such response.
Most notably, the researchers showed that by selectively blocking the expression of cannabinoid receptors on macrophages, they could protect and restore beta cell function in the genetically obese rats, which delayed the development and reduced the severity of their diabetes.
The authors conclude that the findings point to a key role in type 2 diabetes for endocannabinoid-induced inflammasome activation in macrophages, and identify cannabinoid receptors on macrophages as a new therapeutic target.
“To understand type 2 diabetes, a public health threat that affects young and old alike, we need to consider all the factors at play,” said Monica Skarulis, MD, staff clinician at National Institute of Diabetes and Digestive and Kidney Diseases and co-author. “We hope that what we’ve learned from this research will help us develop new strategies to prevent and treat the condition.”
In addition to Dr Kunos’ team of NIAAA scientists and Dr Skarulis, co-authors on the study included researchers from the University of Colorado Medical Campus, Aurora, and the University of Massachusetts Medical School, Worcester.
German biotechnology company BioNTech has stated their intentions to begin production at their mRNA vaccine factory in Rwanda by 2025, which will mark the first foreign mRNA vaccine manufacturing site on the continent of Africa.
A University of Manchester spin-out pharmaceutical company, PharmaKure, has reported successful study results for the quantification of Alzheimer’s Disease biomarker proteins with a whole blood test.
To address vaccine inequality and accessibility issues, the Bill & Melinda Gates Foundation aims to deliver USD $40m to various biotech companies and vaccine manufacturers in support of mRNA vaccine development.
The next episode of the CPHI Podcast Series delves into the science and background behind some recent developments in the field of Alzheimer's disease and neurological disorders.
In this interview with Sandra Sánchez y Oldenhage, President of PharmAdvice, she speaks to the importance of considering patients in the manufacturing stages of the pharmaceutical supply chain, and how it can redefine healthcare.
Artificial intelligence is the topic of debate in the latest episode from the CPHI Podcast Series, where Digital Editor Lucy Chard speaks with Bill Whitford of DPS Group about the integration of AI in healthcare.
Pfizer gains accelerated approval from the US FDA for their new bispecific antibody therapy for multiple myeloma, set to address an unmet need for patients.
Results from the TRAILBLAZER-ALZ 2 Randomised Clinical Trial into the use of donanemab to treat early symptoms of Alzheimer’s disease have been analysed.
Position your company at the heart of the global Pharma industry with a CPHI Online membership
Your products and solutions visible to thousands of visitors within the largest Pharma marketplace
Generate high-quality, engaged leads for your business, all year round
Promote your business as the industry’s thought-leader by hosting your reports, brochures and videos within your profile
Your company’s profile boosted at all participating CPHI events
An easy-to-use platform with a detailed dashboard showing your leads and performance