Diabetics Using Oral Insulin Pill: Reality or Dream

Visualizing how a non-insulin molecule can mimic the role of insulin, a key hormone needed to control blood sugar levels has been demonstrated by a research team in the journal Nature Communications. This study opens new avenues for the development of drugs that could replace daily insulin injections for people with type 1 diabetes.

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Is It Possible to Replace Insulin? A New Study Provides Answers

Researchers in Melbourne have answered a 100-year-old question in diabetes research: can a molecule different from insulin have the same effect? The findings provide important insights for the future development of an oral insulin pill. Researchers have visualized precisely how an insulin-mimicking molecule reproduces the activity of insulin to regulate blood glucose levels. Findings illuminate new opportunities for the development of oral insulin mimetics that may replace daily injections by type 1 diabetics[1].

People with type 1 diabetes cannot produce insulin and require multiple daily insulin injections to keep their blood glucose levels in check [2]. The new research confirms that alternative molecules can be used to turn on blood glucose uptake, bypassing the need for insulin altogether.

The study was led by WEHI’s Dr. Nicholas Kirk and Professor Mike Lawrence, in collaboration with researchers from Lilly, an American-based pharmaceutical company.

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Why is There no Insulin Pill?

Researchers have struggled to make insulin as a pill because insulin is unstable and readily degraded by the body upon digestion. Since the discovery of insulin 100 years ago, the development of an insulin pill has been a dream for diabetes researchers but, after decades of trying, there has been little success[3].

The research has now accelerated dramatically with the development of cryo-electron microscopy (cryo-EM), a new technology that can visualize complicated molecules in atomic detail, allowing researchers to generate 3D images (‘blueprints’) of the insulin receptor rapidly.

With cryo-EM, the direct comparison of how different molecules, including insulin, change the shape of the insulin receptor. Insulin's interaction turns out to be far more complex than anyone predicted, with both insulin and its receptor changing shape dramatically as they partner up.

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Mimicking Insulin with Simple Molecules

The new research shows how an insulin-mimicking molecule acts on the insulin receptor and turns it on, the first step in a pathway that directs cells to soak up glucose when the body’s sugar levels are too high.

The team performed intricate cryo-EM reconstructions to obtain blueprints of several molecules called ‘peptides’ that are known to interact with the insulin receptor and hold it in the ‘active’ position. The cryo-EM experiments identified one peptide that can bind to and activate the receptor like insulin.

While therapeutic outcomes are distant, the team's discovery could lead to a drug to replace insulin, reducing the need for injections by diabetics.

Scientists have had success replacing these kinds of mimetic molecules with drugs that can be taken as pills. It’s still a long road that will require further research, but it’s exciting to know that our discovery opens the door for oral treatments for type 1 diabetes.

References:

1. Kirk, N.S., Chen, Q., Wu, Y.G. et al. Activation of the human insulin receptor by non-insulin-related peptides. Nat Commun. April 2022.(https://www.nature.com/articles/s41467-022-33315-8)
2. National Institute of Diabetes and Digestive and Kidney Diseases.(https://www.niddk.nih.gov/health-information/diabetes/overview/insulin-medicines-treatments)
3. The Global Diabetes Community. Insulin Pills and Tablets.(https://www.diabetes.co.uk/insulin/insulin-pill.html)

Source-Medindia