Pseudoislet system expected to advance pancreas and diabetes research

The multicellular, 3-D structure of human pancreatic islets—the areas of the pancreas containing hormone-producing or endocrine cells—has presented challenges to researchers as they study and manipulate these cells’ function, but Vanderbilt University Medical Center researchers have now developed a pseudoislet system that allows for much easier study of islet function.

A pancreatic islet is composed primarily of beta cells, alpha cells and delta cells, but also includes many supporting cells, such as endothelial cells, nerve fibers and immune cells, which act in concert as a mini organ to control blood glucose through hormone secretion. Insulin, secreted from beta islet cells, lowers blood glucose by stimulating glucose uptake in peripheral tissues, while glucagon, secreted from alpha islet cells, raises blood glucose through its actions in the liver.

Dysfunction of these islet cells is a primary component of all forms of diabetes, and a better understanding of this dysfunction can lead to improved treatment and management of the disease. Vanderbilt scientists and others around the world have identified potential targets for diabetes using both mouse models and human tissue, however the lack of a system to manipulate these pathways in human islet cells has limited the field.

The VUMC team led by Marcela Brissova, Ph.D., research professor of Medicine and director of the Islet Procurement and Analysis Core of the Diabetes Research and Training Center, began attempting a protocol for the pseudoislet system in 2016, performing countless trials. In late 2017, Rachana Haliyur, then a Vanderbilt MD/Ph.D. student, combined media containing factors that support vascular cells and endocrine cells into what the group named the Vanderbilt Pseudoislet Media. The team watched as the cells began reaggregating, or organizing themselves in a way that resembled native islets.

“A lot of things in science happen serendipitously, and this was one of those,” said Brissova. “We tried and failed many times, and basically it came down to the media we used for our cells. In our recent publication, we have provided all experimental details and our protocol so others can make the media and create pseudoislets in their own laboratories.”

Because of the complex structure of the human islet, it is difficult to introduce and manipulate cells past the first cell-layer of the islet sphere. The pseudoislet system allows investigators to separate the pancreatic islet into single cells, introduce a virus into the cells which allows genetic manipulation and then combine the cells back together again into a pseudoislet. This allows researchers to target certain cell types or replicate changes happening in disease and study them in the 3-D environment of the islet.

John “Jack” Walker, an MD/Ph.D. student in the Powers & Brissova Research Group, continued to refine the pseudoislet system protocol and was co-first author on a recent study based on the system published in JCI Insight, an open access journal published by the American Society for Clinical Investigation (ASCI).

The pseudoislet system allowed the VUMC investigators to more clearly examine intracellular signaling pathways, allowing genetic manipulation of those pathways to change their function and better understand how insulin and glucagon secretion are altered with that manipulation. They determined that activation of Gi protein signaling reduced insulin and glucagon secretion while activation of Gq protein signaling stimulated glucagon secretion but had both stimulatory and inhibitory effects on insulin secretion.

In addition, this approach allowed the scientists to introduce biosensors into the islet cells to measure intercellular signaling events within the cells and better understand how those are linked to hormone secretion.

Another advance was the combination of the pseudoislet system with a unique microfluidic device, developed by co-authors Matthew Ishahak and Ashutosh Agarwal, Ph.D., from the University of Miami, that allowed the investigators to simultaneously document the changes in both calcium ions and hormone secretion.

“The exciting thing about this approach is that we both deconstruct the islet for our manipulation and reconstruct it to understand functional consequences at a larger level,” Walker said. “Since we put the islet cells back together, we can look at both insulin and glucagon secretion, but in a coordinated manner. Both of the secretion profiles measured are reflective of intra-islet interactions that are happening as well.”

This work greatly benefited from the research environment and infrastructure at Vanderbilt, particularly the National Institutes of Health (NIH)-funded Diabetes Research and Training Center (DRTC) and the Vanderbilt Cell Imaging Shared Resource.

“Another research direction will be creating pseudoislets that replicate a specific disease state, such as pseudo-islets that look like native islets from an individual with type 1 diabetes,” Haliyur said.

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Diabetes type 2 warning – the two sexual symptoms of high blood sugar you shouldn’t ignore

Diabetes is a common condition that affects more than four million people in the UK, and 90 percent of all cases are caused by type 2 diabetes. You could be at risk of high blood sugar if you develop either of these two symptoms, it’s been claimed.

Type 2 diabetes could be caused by the body not producing enough of the hormone insulin, or the body not reacting to insulin.

Without enough of the hormone, the body struggles to convert sugar in the blood into usable energy.

It’s crucial that if you think you may have diabetes, you speak to a doctor as soon as possible.

You could be at risk of diabetes if you develop erection problems, it’s been revealed.

Struggling to achieve or maintain an erection could be one of the earliest warning signs of high blood sugar, warned Benenden Health’s Society Matron, Cheryl Lythgoe.

It can be caused by damage to the nerves and blood vessels around the penis.

Poor long-term blood sugar control increases the risk of erectile dysfunction.

You should consider speaking to a doctor if you’ve developed problems with an erection.

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“When it comes to diabetes, there are many symptoms that should be getting our attention,” warned Lythgoe.

She told Express Health: “For example, if you struggle with one infection after another – a wound infection that won’t settle or a fungal infection such as thrush or athletes foot for example – this could be a symptom of diabetes.

“As could be episodes of blurred vision, a change to your colour vision or dark ‘floaters’ in the eyes.

“For gents, erectile problems including both achieving and maintaining an erection could also be a symptom.”

But, just because you have an episode of impotence, it doesn’t necessarily mean that you have diabetes.

There are a number of causes for erectile dysfunction that could be remedied with a few lifestyle changes.

Stress, anxiety, or even drinking too much alcohol could all lead to impotence.

You could lower your risk of the symptom by simply losing weight if you’re overweight, eating a healthy diet, and by doing regular exercise.

Many people may have diabetes without even knowing it, because the signs and symptoms don’t necessarily make you feel unwell.

Common diabetes symptoms include having cuts or wounds that take longer to heal, having an unquenchable thirst, and passing more urine than normal.

You should speak to a doctor if you’re worried about the warning signs or symptoms of diabetes, or if you think you may be at risk.

Diagnosing the condition early is very important, because patients are more at risk of some deadly complications, including heart disease and strokes.

Source: Read Full Article

Diabetes type 2 – surprising ‘superfood’ that could lower your risk of high blood sugar

Diabetes is a common condition that affects more than four million people in the UK, and 90 percent of all cases are caused by type 2 diabetes. You could lower your risk of high blood sugar by regularly eating full-fat Greek yoghurt, it’s been claimed.

Type 2 diabetes could be caused by the body not producing enough of the hormone insulin, or the body not reacting to insulin.

Without enough of the hormone, the body struggles to convert sugar in the blood into usable energy.

It’s crucial that if you think you may have diabetes, you speak to a doctor as soon as possible.

Making some changes to your daily diet is one of the easiest ways to manage your blood sugar levels.

Greek yoghurt is a complex superfood that’s low in sugar and carbohydrates, while being rich in protein.

Full-fat yoghurt is the better option for diabetes patients, compared to low-fat varieties, according to medical website Diabetes.co.uk.

People that eat the most Greek yoghurt have the lowest risk of insulin resistance, as well as lower blood sugar levels, scientists have added.

You can combine your Greek yoghurt with nuts and berries for the largest diabetes benefits.

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“There are certain foods that provide huge health benefits for people with diabetes,” said Diabetes.co.uk. “They are often known as ‘diabetes superfoods’.

“Greek yoghurt is one of the more complex ‘superfoods’. Certainly, it has its benefits – it’s low-carb, high-protein, and low in sugar – but the debates regarding fat content can be confusing.

“Full-fat Greek yoghurt is better for people with diabetes, which may sound strange but fat’s bad reputation isn’t justified.

“This is because there are different kinds of saturated fat. Essentially, some saturated fat particles increase the risk of heart disease, and some don’t.”

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But, if you decide to have Greek yoghurt for breakfast, you should avoid having fruit juices as an accompanying drink, warned the medical website.

Diabetes patients should limit the amount of fruit juices in their diet, it urged.

Although it’s previously been considered a healthy option, fruit juice may contain large amounts of sugar.

The sugar could directly increase blood sugar levels in diabetes patients, which may lead to hyperglycaemia.

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  • Type 2 diabetes: Sign in your breath

Many people may have diabetes without even knowing it, because the signs and symptoms don’t necessarily make you feel unwell.

Common diabetes symptoms include having cuts or wounds that take longer to heal, having an unquenchable thirst, and passing more urine than normal.

You should speak to a doctor if you’re worried about the warning signs or symptoms of diabetes, or if you think you may be at risk.

Diagnosing the condition early is very important, because patients are more at risk of some deadly complications, including heart disease and strokes.

Source: Read Full Article