New diabetes treatment could eliminate need for insulin injections
A cell-based diabetes treatment has been developed by scientists who
say it could eliminate the need for those with the condition to inject
insulin.
The therapy involves a capsule of genetically engineered cells implanted under the skin that automatically release insulin as required. Diabetic mice that were treated with the cells were found to have normal blood sugar levels for several weeks.
Scientists said they hope to obtain a clinical trial licence to test the technology in patients within two years. If successful, the treatment would be relevant for all type 1 diabetes patients, as well as those cases of type 2 diabetes that require insulin injections.
Martin Fussenegger, who led the research at the ETH university in Basel, said: “By 2040, every tenth human on the planet will suffer from some kind of diabetes, that’s dramatic. We should be able to do a lot better than people measuring their glucose.”
Fussenegger said that, if confirmed as safe and effective in humans, diabetes patients could be given an implant that would need to be replaced three times a year rather than injections, which do not perfectly control blood sugar levels, leading to long-term complications including eye, nerve and heart damage.
In Britain, about 400,000 people have type 1 diabetes and three million have type 2 diabetes, about 10% of whom need to inject insulin to control the condition.
Type 1 diabetes normally begins in childhood and is an autoimmune disease in which the body kills off all its pancreatic beta cells. The cells respond to the body’s fluctuating glucose levels by releasing insulin, which regulates blood sugar. Without beta cells, patients need to monitor glucose and inject insulin as required – typically several times each day.
Previously, scientists have attempted to artificially cultivate pancreatic cells from patients’ stem cells. However, scientists have struggled to manufacture the cells at the scale necessary for clinical use, and the cells are naturally prone to dying off once introduced into the body, according to Fussenegger. “They are prima donnas in the cellular context,” he said.
His team took a different approach, choosing to re-engineer human kidney cells, known as HEK cells, to perform the function normally carried out by the pancreas. Two genes were introduced into the cells – one to make them sensitive to glucose levels and a second to instruct the cell to pump out insulin when glucose levels exceeded a threshold.
“We believed we needed a more robust cell type if you go for cell-based therapies,” he said.
In the study, published in Science, the engineered HEK cells were found to outperform normal pancreatic cells in terms of their ability to regulate blood sugar in mice. They were healthy three weeks after the implant and performed normally on various tests designed to measure their ability to control blood sugar.
“It’s hard to understand why ours should be better than something that evolved for millions of years,” said . “It shows that as engineers, thinking rationally, we can also do a very good job.”
In the study, mice were treated such that they lost all their insulin-producing pancreatic cells. The cells were then implanted into the mice, enclosed in a teabag-like porous capsule that protected the human cells from the mouse immune system, but allowed insulin to diffuse out.
In humans, the same approach would mean cells would not need to be genetically matched to the patient, and frozen capsules could be manufactured on an industrial scale.
The team behind the work have created a start-up to commercialise the technique and hope it could reach the market within a decade.
Emily Burns, research communications manager at Diabetes UK, said: “We can already replace the cells in the pancreas that are damaged in type 1 diabetes by using cells taken from donated pancreases, but one of the issues with this approach is that there aren’t enough donors. That’s why research like this is so important: finding ways to produce an unlimited supply of pancreatic cells, or cells that act like them, in the lab.”
Insulin resistance - a condition where the body's cells fail to
respond normally to the glucose control hormone insulin - increases the
risk of developing type 2 diabetes and prediabetes. Now, a team shows
that removing or blocking a protein mainly secreted by immune cells
reverses diabetic insulin resistance and glucose intolerance in obese
and diabetic mice.
The researchers say that the high levels of macrophages - a type of immune cell - in fat tissue promotes chronic inflammation and insulin resistance.
The team - including researchers from the University of
California-San Diego (UCSD) - reports what it discovered about the
protein galectin-3 or Gal3 in the journal Cell.
Senior author Jerrold Olefsky, a professor of medicine at UCSD School of Medicine, remarks:
"This study puts Gal3 on the map for insulin resistance and diabetes in mouse model."
Insulin is a hormone that the body uses to control glucose or blood sugar. Diabetes is a chronic disease that arises either when the pancreas does not make enough insulin (known as type 1 diabetes) or when the body cannot use the insulin it produces properly (type 2 diabetes).
Most people with diabetes have type 2 diabetes, largely due to excess body weight and physical inactivity.
Until recently, type 2 diabetes was only seen in adults, but now more and more children are developing it.
If diabetes goes untreated, there is a high chance of hyperglycemia, or raised blood sugar, which over time causes serious damage to vital parts of the body, including nerves and blood vessels.
In 2014, global estimates suggest 8.5 percent of adults were living with diabetes - up from 4.7 percent in 1980. In 2012, an estimated 1.5 million people died as a direct result of diabetes, and another 2.2 million as a result of high blood glucose.
Rates of diabetes have been rising more rapidly in middle- and low-income countries. In the United States, rates of new cases of diagnosed diabetes have started to fall, but the numbers are still very high.
Over 29 million Americans are thought to have diabetes, and 86 million have prediabetes - a serious condition that raises the risk of developing type 2 diabetes and other chronic diseases.
In obese humans and mice, macrophages and other immune cells accumulate in fat tissue. The researchers note that around 40 percent of cells in fat tissue in obese subjects are macrophages.
The high levels of these immune cells in the fat tissue promotes "a chronic inflammatory state and insulin resistance," they write, adding that obese mice and humans also have high levels of Gal3 - a signaling protein secreted by macrophages.
The secretion of Gal3 attracts more macrophages, setting up a vicious cycle that results in ever-increasing levels of the signaling protein and accumulation of the immune cells.
In lab experiments, the researchers found that Gal3 was produced by bone marrow-derived macrophages and that secretion of the protein leads to insulin resistance in liver, muscle, and fat cells - even when there is no inflammation.
They also found giving mice Gal3 leads to insulin resistance and glucose intolerance, while blocking it in obese mice - either with drugs or by silencing a gene - improves insulin sensitivity.
"Importantly," note the authors, "we found that Gal3 can bind directly to the insulin receptor (IR) and inhibit downstream IR signaling."
Other studies have already linked Gal3 to other diseases. The team now plans to find out if the signaling protein could be a target for the treatment of conditions such as nonalcoholic fatty liver disease and heart and liver fibrosis.
The therapy involves a capsule of genetically engineered cells implanted under the skin that automatically release insulin as required. Diabetic mice that were treated with the cells were found to have normal blood sugar levels for several weeks.
Scientists said they hope to obtain a clinical trial licence to test the technology in patients within two years. If successful, the treatment would be relevant for all type 1 diabetes patients, as well as those cases of type 2 diabetes that require insulin injections.
Martin Fussenegger, who led the research at the ETH university in Basel, said: “By 2040, every tenth human on the planet will suffer from some kind of diabetes, that’s dramatic. We should be able to do a lot better than people measuring their glucose.”
Fussenegger said that, if confirmed as safe and effective in humans, diabetes patients could be given an implant that would need to be replaced three times a year rather than injections, which do not perfectly control blood sugar levels, leading to long-term complications including eye, nerve and heart damage.
In Britain, about 400,000 people have type 1 diabetes and three million have type 2 diabetes, about 10% of whom need to inject insulin to control the condition.
Type 1 diabetes normally begins in childhood and is an autoimmune disease in which the body kills off all its pancreatic beta cells. The cells respond to the body’s fluctuating glucose levels by releasing insulin, which regulates blood sugar. Without beta cells, patients need to monitor glucose and inject insulin as required – typically several times each day.
Previously, scientists have attempted to artificially cultivate pancreatic cells from patients’ stem cells. However, scientists have struggled to manufacture the cells at the scale necessary for clinical use, and the cells are naturally prone to dying off once introduced into the body, according to Fussenegger. “They are prima donnas in the cellular context,” he said.
His team took a different approach, choosing to re-engineer human kidney cells, known as HEK cells, to perform the function normally carried out by the pancreas. Two genes were introduced into the cells – one to make them sensitive to glucose levels and a second to instruct the cell to pump out insulin when glucose levels exceeded a threshold.
“We believed we needed a more robust cell type if you go for cell-based therapies,” he said.
In the study, published in Science, the engineered HEK cells were found to outperform normal pancreatic cells in terms of their ability to regulate blood sugar in mice. They were healthy three weeks after the implant and performed normally on various tests designed to measure their ability to control blood sugar.
“It’s hard to understand why ours should be better than something that evolved for millions of years,” said . “It shows that as engineers, thinking rationally, we can also do a very good job.”
In the study, mice were treated such that they lost all their insulin-producing pancreatic cells. The cells were then implanted into the mice, enclosed in a teabag-like porous capsule that protected the human cells from the mouse immune system, but allowed insulin to diffuse out.
In humans, the same approach would mean cells would not need to be genetically matched to the patient, and frozen capsules could be manufactured on an industrial scale.
The team behind the work have created a start-up to commercialise the technique and hope it could reach the market within a decade.
Emily Burns, research communications manager at Diabetes UK, said: “We can already replace the cells in the pancreas that are damaged in type 1 diabetes by using cells taken from donated pancreases, but one of the issues with this approach is that there aren’t enough donors. That’s why research like this is so important: finding ways to produce an unlimited supply of pancreatic cells, or cells that act like them, in the lab.”
The researchers say that the high levels of macrophages - a type of immune cell - in fat tissue promotes chronic inflammation and insulin resistance.
Senior author Jerrold Olefsky, a professor of medicine at UCSD School of Medicine, remarks:
"This study puts Gal3 on the map for insulin resistance and diabetes in mouse model."
Insulin is a hormone that the body uses to control glucose or blood sugar. Diabetes is a chronic disease that arises either when the pancreas does not make enough insulin (known as type 1 diabetes) or when the body cannot use the insulin it produces properly (type 2 diabetes).
Most people with diabetes have type 2 diabetes, largely due to excess body weight and physical inactivity.
Until recently, type 2 diabetes was only seen in adults, but now more and more children are developing it.
If diabetes goes untreated, there is a high chance of hyperglycemia, or raised blood sugar, which over time causes serious damage to vital parts of the body, including nerves and blood vessels.
In 2014, global estimates suggest 8.5 percent of adults were living with diabetes - up from 4.7 percent in 1980. In 2012, an estimated 1.5 million people died as a direct result of diabetes, and another 2.2 million as a result of high blood glucose.
Rates of diabetes have been rising more rapidly in middle- and low-income countries. In the United States, rates of new cases of diagnosed diabetes have started to fall, but the numbers are still very high.
Over 29 million Americans are thought to have diabetes, and 86 million have prediabetes - a serious condition that raises the risk of developing type 2 diabetes and other chronic diseases.
Giving mice Gal3 leads to insulin resistance
Like other researchers, Prof. Olefsky has been looking into how insulin resistance in type 2 diabetes can develop from chronic tissue inflammation.
Fast facts about diabetes
In the new study, he and his colleagues explain how immune cells
called macrophages - which destroy targeted cells - play an important
role in inflammation.- People with diabetes are twice as likely to have heart disease or a stroke as people without diabetes
- Up to 25 percent of American adults who have diabetes don't know they have it or realize they could be developing serious complications
- More than a fifth of healthcare spending in the U.S. goes on people with diagnosed diabetes.
In obese humans and mice, macrophages and other immune cells accumulate in fat tissue. The researchers note that around 40 percent of cells in fat tissue in obese subjects are macrophages.
The high levels of these immune cells in the fat tissue promotes "a chronic inflammatory state and insulin resistance," they write, adding that obese mice and humans also have high levels of Gal3 - a signaling protein secreted by macrophages.
The secretion of Gal3 attracts more macrophages, setting up a vicious cycle that results in ever-increasing levels of the signaling protein and accumulation of the immune cells.
In lab experiments, the researchers found that Gal3 was produced by bone marrow-derived macrophages and that secretion of the protein leads to insulin resistance in liver, muscle, and fat cells - even when there is no inflammation.
They also found giving mice Gal3 leads to insulin resistance and glucose intolerance, while blocking it in obese mice - either with drugs or by silencing a gene - improves insulin sensitivity.
"Importantly," note the authors, "we found that Gal3 can bind directly to the insulin receptor (IR) and inhibit downstream IR signaling."
Other studies have already linked Gal3 to other diseases. The team now plans to find out if the signaling protein could be a target for the treatment of conditions such as nonalcoholic fatty liver disease and heart and liver fibrosis.
"Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach."Learn how a key to faster-acting insulin was found in snail venom.
Prof. Jerrold Olefsky
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