The “Smart” Insulin

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insulin molecule
Model of insulin hinge reacting to sugar. Source: Indiana University School of Medicine

Type 1 diabetes is a chronic disease caused by insufficient production of a hormone called “insulin” which regulates blood glucose levels in the body. This occurs due to the destruction of insulin-producing beta cells, situated in the islets of Langerhans in the pancreas.


The most common cause of this disease is autoimmune- the body’s immune system attacks beta cells, mistaking them for pathogens. Viruses, such as Coxsackievirus B, mumps, rotavirus, and cytomegalovirus may also trigger the development of type 1 diabetes.


A potentially fatal disease


Insulin works in conjunction with another hormone called glucagon to regulate a process called glucose homeostasis. It works like this: increased levels of blood glucose triggers beta cells, which produce insulin. The hormone works to lower these levels in the blood by increasing glucose uptake into specialized cells. These cells convert glucose into glycogen or triglycerides for storage, ready for release once the body’s supply grows low. That, is a job for glucagon.


In type 1 diabetes, insulin’s absence causes glucose to circulate in the blood unchecked. If levels grow too high, it can cause hyperglycemia: dehydration, blurred vision, headaches. A more severe symptom occurs when the body switches to breaking down fat for fuel through ketogenesis. This produces acidic ketone bodies, which lowers blood pH, causing an acute and potentially life-threatening condition called Diabetic Ketoacidosis (DKA).


So how do you treat type 1 diabetes?


Currently, the only treatment available for this disease is palliative care through diet, exercise, and insulin replacement. Patients with type 1 diabetes have to constantly monitor their glucose level throughout the day to make sure it stays within prescribed limits. This is a difficult procedure because, while too little insulin is indeed dangerous, too much will cause hypoglycemia: fatigue, sweating, tachycardia, which if prolonged, can cause seizures and loss of consciousness.


The “smart” Insulin


In a bid to help patients navigate insulin therapy more easily and efficiently, scientists from the School of Medicine at Indiana University decided to chemically modify normal insulin so that the hormone’s molecules themselves become sensitive to the levels of glucose in the blood.


The team, headed by Professor Michael A. Weiss, made use of the hormone’s structure, which includes a “protective hinge” that when closed keeps the hormone stable, and when opened, allows the hormone to function properly.
Once modified, the sensitive hormones opened or closed their hinge to match the level of glucose, decreasing chances of fluctuation.


The team tested their invention using fructose and found that the “switch” does indeed work. They now intend to create molecules sensitive to glucose, the real breakthrough.


“While the current analog has been designed to sense fructose, it seems likely that this same approach can be used to develop analogs to sense glucose. Whether these can be sensitive enough to be modulated by changes within the physiological range remains to be determined, but if so, this would be an important new tool in the management of diabetes.”

RONALD KAHN, MD, JOSLIN DIABETES CENTER AT HARVARD MEDICAL SCHOOL.

Source: University of Indiana School of Medicine
https://medicine.iu.edu/news/2021/07/Synthetic-hinge-could-hold-key-to-revolutionary-smart-insulin-therapy
WebMD
https://www.webmd.com/diabetes/type-1-diabetes

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