Diabetes drug dulaglutide may reduce symptoms of depression

Published

1 year ago

March 8, 2024

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By Dr. Priyom Bose, Ph.D. Mar 8 2024 Reviewed by Danielle Ellis, B.Sc.

A recent Brain and Behavior study investigated the antidepressant effect of dulaglutide and the mechanism that underlies this effect. Study: Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress. Image Credit: luchschenF/Shutterstock.com Background

Depression is a chronic mood disorder that is associated with low mood, insomnia, weight loss, a state of unhappiness, aversion to activity, fatigue, and low self-esteem. According to the World Health Organization, depression has become one of the major health burdens across the world.

This mental health condition is commonly treated with an antidepressant that takes around a month to alleviate the symptoms. However, several side effects are associated with the use of antidepressant drugs and could be toxic at high doses.

A combination of psychological, genetic, and neurological factors contributes to the manifestations of depression. Even though the exact etiology of this mental health issue is not fully understood, research has shown chronic stress to be an inducer of depression.

The hippocampus is a region of the brain that is associated with depression and modifies functionally and morphologically in response to stress. Animal model studies have shown that a decrease in neuronal and glial size, reduction in synaptic markers, loss of dendrites, and increase in apoptosis in the hippocampus leads to depression.

Many studies have uncovered the metabolic aspects of depression. For instance, diabetes and obesity are two common metabolic disorders that increase the risk of depression. Considering its high prevalence, novel therapies with high efficacy and fewer side effects are required to combat depression. The chronic mild stress (CMS) model has been recognized as a reliable rodent model to study depression.

Glucagon-like peptide-1 (GLP-1) and its receptor agonists are involved with anti-inflammatory effects and neuroprotective activities and can improve mental disorders, particularly depression and cognition. GLP-1 is a peptide hormone that stimulates the secretion of insulin and restricts the synthesis of glucagon in the pancreas in a glucose-dependent manner. Liraglutide is a GLP-1 analog that exhibited a positive effect in reducing anxiety and depression symptoms.

Dulaglutide is a novel long-acting GLP-1 receptor agonist that improves cognitive dysfunction and neuronal damage in rats with vascular dementia. Although many studies highlighted the efficacy of dulaglutide in preventing depression-like behavior triggered by chronic social defeat stress (CSDS), the underlying mechanism of this effect is not clearly understood. About the study

The current study used a metabolomics strategy to evaluate the effect of dulaglutide in a CMS model. Furthermore, the underlying mechanism of this effect was also assessed. Adult male ICR mice, which is a strain of albino mice, were selected for this study. All test mice were around seven weeks old.

After one week of acclimatization, 60 mice were randomly assigned in four groups, namely, control (CON), the CMS and Vehicle group (CMS+Veh), the CMS and 0.3 mg/kg dulaglutide group (Low Dula), and the CMS and 0.6 mg/kg dulaglutide group (High Dula). Except for the CON group, all other groups were exposed to stressors. Related StoriesSugar tax shows sweet results in cutting obesity and diabetes ratesAI-based model enhances efficiency of Type II diabetes prevention effortsStudy reveals mechanisms behind antidepressant effects of diabetes drug

To establish the CMS model of depression, selected mice were exposed to two or three different stressors for 28 days continuously. For stress induction, mice were deprived of water and food for 12 hours, kept in wet bedding for 24 hours, kept in a tilted cage for 24 hours, pintail for 1 minute, and cold water treatment for five minutes. The body weight of each test mouse was measured weekly, and behavioral tests, such as the tail suspension test (TST), open field test (OFT), and forced swimming test (FST), were performed. Study findings

The mice subjected to CMS for four weeks exhibited depressive- and anxiety-like symptoms. An LC-MS/MS metabolomics study was performed to understand the potential pathophysiological mechanisms and investigate the efficacy of drugs to alleviate depression-like symptoms.

A distinct difference between the CON group, CMS+Veh group, and High Dula group was observed in accordance with the metabolic disorders induced by chronic stress, which was altered through dulaglutide treatment. Many potential biomarkers were identified that are associated with purine metabolism, arginine and proline metabolism, glycerophospholipid metabolism, glutamate metabolism, sphingolipid metabolism, and bile secretion.

Lipid metabolism pathways could be potential targets through which dulaglutide alleviates depression. Lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), phosphatidylinositol (PI), sphingolipids, and phosphatidylcholine (PC), are involved with the therapeutic effect of dulaglutide in alleviating depression. Consistent with previous studies findings, this study highlighted the association between lipid metabolism and the antidepressant effect of dulaglutide.

The current study indicated the downregulation of N-acetyl-L-aspartic acid (NAA) in the CMS model group. NAA, which is one of the most important metabolites of the vertebrate nervous system, was found in decreased levels in rats with chronic, unpredictable, mild stress. However, the current study indicated that dulaglutide therapy increased the levels of NAA through its upregulation in the hippocampus.

In the CMS model group, an upregulation in L-glutamic acid and L-arginine was observed. Dulaglutide treatment caused a decrease in arginine and proline, thereby indirectly exhibiting a neuroprotective effect. Conclusions

The current study highlighted the antidepressant effects of dulaglutide using the CMS depression model. Notably, the potential metabolisms that underlie the antidepressant effect of dulaglutide have been elucidated in this study. Journal reference: Jin, M., Zhang, S., Huang, B., Li, L., Liang, H., Ni, A., Han, L., Liang, P., Liu, J., Shi, H. and Lv, P. (2024) Brain and Behavior, 14(3). doi: 10.1002/brb3.3448. https://onlinelibrary.wiley.com/doi/10.1002/brb3.3448?utm_medium=email

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Migrants locked up in notorious El Salvador jail released in Venezuela-US prisoner swap

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2 hours ago

July 20, 2025

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Migrants locked up in notorious El Salvador jail released in Venezuela-US prisoner swap

On Friday, Paola Paiva waited in a hotel near Caracas airport, nervous but giddy with excitement to be reunited with her brother, finally.

For five months, Arturo Suarez has been detained in a notorious prison in El Salvador.

“I am going to wait for my brother to call me,” she told Sky News, “and after giving him a hug, I want to just listen to him, listen to his voice. Let him talk and tell us his story.”

Suarez was one of the more than 250 Venezuelan migrants who had been living in America but were arrested in immigration raids by the Trump administration and sent to El Salvador, a showpiece act in the president’s promise to deport millions of migrants.

Most of the men had never even been to El Salvador before. Their detention has been controversial because the White House claims the men are all part of the dangerous Tren de Aragua gang but has provided little evidence to support this assertion.

The only evidence Paola had that Suarez was still alive was a picture of him published on a news website showing the inside of the maximum security CECOT jail.

He is one of dozens of men with their hands and feet cuffed, heads shaved and bodies shackled together.

Now he is returning to his home country, one of the bargaining chips in a deal that saw the release of ten Americans and US permanent residents who had been seized by the Venezuelan authorities.

Paola had tried to go to the airport to greet her brother as he disembarked a charter plane bringing the men back from El Salvador but authorities told her to wait at a nearby hotel.

“They told us they are taking them all to a hotel to rest,” she said.

“But I managed to get someone to give my phone number on a piece of paper to my brother, so I am expecting his call tomorrow, as soon as he can access a phone.

“We heard they are going to perform some medical exams on them and check their criminal records,” she added. “I’m not afraid; I’m not worried since my brother has a clean record.

“I am so happy. I knew this day would happen, and that it would be unexpected, that no one was going to notify us. I knew it was going to be a total surprise.”

The Trump administration had paid the El Salvador government, led by President Nayib Bukele, millions of dollars to imprison the men.

Homeland security secretary Kristi Noem visited CECOT last month, posing in front of prisoners for a photo opportunity.

But Cristosal, an international human rights group based in El Salvador, says it has “documented systematic physical beatings, torture, intentional denial of access to food, water, clothing, health care,” inside the prison.

A video which was seemingly filmed aboard the charter flight bringing the Venezuelan migrants back to Caracas shows Arturo briefly talking about his experience inside.

He looks physically well but speaks into the camera and says: “We were four months with no communication, no phone calls, kidnapped, we didn’t know what (the) day was, not even the time.

“We were beat up at breakfast, lunch and dinner,” he continues.

Sky News interviewed Arturo Suarez‘s brother Nelson near his home in the US in April, weeks after Arturo – an aspiring singer – had been arrested by immigration and customs enforcement (ICE) agents while filming a music video inside a house.

Nelson said he believed Arturo’s only crime was “being Venezuelan and having tattoos.” He showed me documents that indicate Arturo has no criminal record in Venezuela, Chile, Colombia or the United States, the four countries he has lived in.

Now Nelson is delighted Arturo is being released – but worries for his future.

“The only thing that casts a shadow in such a moment of joy is that bit of anger when I think that all the governments involved are going to use my brother’s story, and the others on that flight, as political gain,” he said.

“Each of them will tell a different story, making themselves the heroes, when the reality is that many innocent people suffered unfairly and unnecessarily, and many families will remain separated after this incident due to politics, immigration and fear.”

World

Ha Long Bay: At least 34 dead after tourist boat capsizes in Vietnam

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2 hours ago

July 20, 2025

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Ha Long Bay: At least 34 dead after tourist boat capsizes in Vietnam

At least 34 people have died after a tourist boat capsized in Vietnam, according to state media reports.

The Wonder Sea boat was reportedly carrying 53 people, including five crew members, when it capsized due to strong winds in Ha Long Bay on Saturday.

It happened at roughly 2pm local time (7am GMT). Rescue teams have found 11 survivors and recovered 34 bodies, eight of them children, the state-run Vietnam News Agency said, citing local authorities.

The People’s Army Newspaper, which cited local border guards, said authorities have not yet confirmed details about the tourists, including their nationalities, as the rescue operation continues.

Most of the passengers were tourists, including about 20 children, from the country’s capital city, Hanoi, the newspaper said.

The incident comes shortly after the arrival of Storm Wipha in the South China Sea, bringing strong winds, heavy rain and lightning to the area.

The named storm is the third typhoon to hit the South China Sea this year, and is expected to make landfall along the northern coast of Vietnam early next week.

Disruptions linked to the storm have also had an impact on air travel, according to Noi Bai Airport.

The airport reported that nine incoming flights were diverted to other airports, while three outgoing flights were temporarily grounded due to adverse weather conditions.

The winds brought by Storm Wipha reached up to 63mph (101kmph) and gusts of up to 68mph (126kmph) as it passed south of Taiwan on Saturday, according to the island’s Central News Agency.

Ha Long Bay is around 125mi (200km) north east of Hanoi and attracts tens of thousands of visitors each year.

Of those who visit Ha Long Bay, many choose to take overnight boat tours to further explore the area.

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Gaza: More than 30 people killed ‘as Israeli troops open fire towards Palestinians waiting for aid’

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2 hours ago

July 20, 2025

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Gaza: More than 30 people killed 'as Israeli troops open fire towards Palestinians waiting for aid'

More than 30 people have been killed after Israeli troops opened fire towards crowds of Palestinians waiting for aid, according to witnesses and hospital officials.

The deaths occurred near distribution hubs operated by the US-Israeli-backed Gaza Humanitarian Foundation (GHF), which began distributing food packages in Gaza at the end of May, after Israel eased its 11-week blockade of aid into the territory.

At least 32 people were killed on Saturday, according to the Hamas-run Gaza health ministry, while a further 100 people were injured, according to local reports.

Most of the deaths came as Palestinians massed in the Teina area, around 3km (2 miles) away from a GHF aid distribution centre east of the city of Khan Younis.

Mahmoud Mokeimar said he was walking with crowds of people – mostly young men – towards the food hub when troops fired warning shots as the crowd advanced, before opening fire towards the marching people.

“It was a massacre… the occupation opened fire at us indiscriminately,” he said.

Akram Aker said troops fired machine guns mounted on tanks and drones.

“They encircled us and started firing directly at us,” he said.

The Nasser Hospital in Khan Younis said it received 25 bodies, along with dozens of wounded.

Seven other people, including one woman, were killed in the Shakoush area, hundreds of yards north of another GHF hub in Gaza’s southernmost city of Rafah, the hospital said.

The army and GHF did not immediately comment on Saturday’s violence.

The GFH, which has four distribution centres, three of which are in the southern Gaza Strip, says it has distributed millions of meals to hungry Palestinians.

But local health officials and witnesses say hundreds of people have been killed by Israeli army fire as they try to reach the distribution hubs.

The GHF, which employs private armed guards, says there have been no deadly shootings at its sites, though this week, 20 people were killed at one of its locations, most of them in a stampede.

The group accused Hamas agitators of causing a panic, but gave no evidence to back the claim.

The army, which is not at the sites but secures them from a distance, says it only fires warning shots if crowds get too close to its forces.

The 21-month war in Gaza was triggered when Hamas militants stormed into southern Israel on 7 October 2023, killing 1,200 people and taking 250 others hostage.

An Israeli military offensive has killed more than 58,000 Palestinians, according to the Gaza health ministry, while Gaza’s more than two million Palestinians are living through a catastrophic humanitarian crisis.

Israel and Hamas have been holding ceasefire talks in Qatar in recent weeks, but international mediators say there have been no breakthroughs.

US President Donald Trump said another 10 hostages will be released from Gaza shortly, without providing details.