Glucagon - Diabetes Research Connection

Diabetes Research News
July 14, 2020

Combination Therapy May Help Improve Blood Sugar Management

Maintaining stable blood sugar levels and minimizing complications is a constant challenge for many individuals living with type 1 diabetes. They must always be alert to whether their blood sugar is too low or too high and how much insulin to administer. However, researchers are continually exploring ways to improve blood sugar management by better understanding how diabetes affects the body.

In a recent study, researchers from Stanford University have taken a new approach by combining two FDA-approved drugs and developing a way for them to work in tandem as they naturally do in the body through a single injection. In addition to insulin, individuals with type 1 diabetes (T1D) would also take a drug based on the hormone amylin. This drug is already FDA-approved, but less than 1% of patients with diabetes take it. This could be because they do not want to administer a second shot every time they take insulin. When combined, insulin and the amylin-based drug work together just as they do when naturally occurring in the body. Amylin is produced by the same insulin-producing beta cells in the pancreas.

According to researchers, amylin works in three ways:

“First, it stops another hormone, glucagon, from telling the body to release additional sugar that has been stored in the liver. Second, it produces a sense of “fullness” at mealtimes that reduces food intake. Third, it actually slows the uptake of food by the body, reducing the typical spike in blood sugar after a meal. All three are a boon to diabetes care.”

However, in their current states, insulin and the amylin-based drug are too unstable to combine in one syringe. To combat this problem, the researchers have developed a protective coating that encompasses each molecule individually, allowing them to stably exist together. This molecular wrapper has a Velcro-like feature that “reversibly binds to both insulin and amylin separately, shielding the unstable portion of each molecule from breakdown.” Once administered, the coating dissolves in the bloodstream.

With this protective coating – known as cucurbituril-polyethylene glycol (CB-PEG) – the combination of insulin and the amylin-based drug showed stability for at least 100 hours. This could give it a shelf life that is long enough to be used with an insulin pump. Researchers have tested the combination therapy on diabetic pigs and are working toward gaining approval for human trials. Since both drugs are already FDA-approved, this could help to move things along more quickly.

Diabetes Research Connection (DRC) is excited to see what this could mean for the future of T1D treatment and blood glucose management. This combination therapy could help alleviate some of the challenges that patients face and improve management of the disease. Though not involved with this study, the DRC is committed to supporting research around type 1 diabetes in order to improve diagnosis, treatment, prevention, and the pursuit of a cure. The organization provides critical funding to early-career scientists to advance their research. Click to learn more about current projects and provide support.

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Diabetes Research News
July 7, 2020

Targeting the Effects of Specific Drugs on Pancreatic Islets

The production of insulin and glucagon used to regulate blood sugar levels come from pancreatic islet cells. In individuals with type 1 diabetes, the immune system mistakenly attacks and destroys these cells leaving the body unable to naturally regulate blood sugar. That means that individuals must continuously monitor and manage these levels themselves.

A recent study examined the impact that specific drugs have on pancreatic islet cells and their function. Researchers were able to fine-tune single-cell transcriptomics to remove contamination from RNA molecules that could interfere with results and negatively affect reliability of the data.

Once they had created decontaminated transcriptomes, they tested three different drugs that relate to blood glucose management. They found that one drug, FOXO1, “induces dedifferentiation of both alpha and beta cells,” while the drug artemether “had been found to diminish the function of alpha cells and could induce insulin production in both in vivo and in vitro studies.” They compared these drugs in both human and mouse samples to determine if there were any differences in how the cells responded. One notable difference was that artemether did not have a significant impact on insulin expression in human cells, but in mouse cells, there was reduced insulin expression and overall beta cell identity.

Single-cell analysis of various drugs could help guide future therapeutic treatments for type 1 diabetes as researchers better understand their impact. Targeted therapies have become a greater focus of research as scientists continue to explore T1D at a cellular level.

Diabetes Research Connection (DRC) is interested to see how single-cell sequencing and the ability to decontaminate RNA sequences could affect diabetes research. The organization supports a wide array of T1D-focused studies by providing critical funding to allow early-career scientists to advance their research. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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Diabetes Research News
August 5, 2019

Nasal Glucagon Approved to Treat Severe Hypoglycemia

If you or someone you love is living with type 1 diabetes, you know that, in addition to blood sugar becoming too high, having it drop too low is a serious concern as well. When blood sugar falls below 70mg/dL, individuals often start feeling the effects such as shakiness, sweating, chills, lightheadedness, weakness, blurry vision, or tiredness.

If blood sugar continues to drop, it can lead to severe hypoglycemia where the person may be unable to treat their low blood sugar themselves due to confusion, seizures, or loss of consciousness. When this occurs, the individual with T1D often relies on medical personnel or a trained bystander to administer glucagon. Traditionally, glucagon is injected into the arm, thigh, or buttock. However, the medication must first be reconstituted, which involves injecting the contents of the syringe into a vial, mixing it together, then drawing it back into the syringe to inject into the person. In an emergency situation, this can be a lot of steps to follow and there is plenty of room for error.

In an effort to simplify the process, Eli Lilly and Company has manufactured the first ever FDA-approved nasal glucagon, Baqsimi. The device is pre-loaded with 3 mg of glucagon and ready to use for patients age 4 and older. The medication stimulates the liver to release glucose and was found to effectively reverse insulin-induced hypoglycemia based on three studies encompassing more than 200 participants. There were no major safety concerns, and the potential adverse reactions were similar to those of injectable glucagon with the addition of watery eyes and nasal congestion. However, nasal glucagon is not recommended for individuals with pheochromocytoma or insulinoma.

Nasal glucagon provides yet another option for individuals with T1D to quickly – and more easily – treat episodes of severe hypoglycemia. It is simple to use because there is no reconstitution, multi-step processes, or injections necessary. The drug is expected to hit the U.S. market around the beginning of September 2019.

We are excited to see this new product come to market and is interested to see how it impacts diabetes care and management for individuals who experience severe hypoglycemia.

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