MicroRNA Control Method to Enhance Pancreatic Receptor Protein Production Improves Effectiveness of Diabetes Meds
등록일 2019년 01월 07일 목요일
수정일 2017년 11월 09일 목요일

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A new research found a method on how to increase the effectiveness of diabetes drugs and how to reduce their side effects.Researchers at the University of Alabama at Birmingham discovered that a molecule called microRNA-204 inhibits insulin production of beta cells of the pancreas.

The research group led by Dr.Anath Shalev, an endocrinologist at the University of Alabama at Birmingham, found a purpose for miR-204, then created drugs that inhibit it and regulate the glucagon-like peptide 1 receptor.

"This novel concept of inhibiting a microRNA in a non-targeted manner, but taking advantage of its restricted tissue distribution and thereby selectively upregulating its target genes in that tissue, may have far-reaching implications for microRNA biology and tissue-specific gene targeting in general," said Dr.Shalev.

Photo by: Alexilusmedical via Shutterstock

Healthy beta cells are found in the pancreatic islets and their job is to control blood sugar levels by secreting insulin.Diabetic people have beta cells that are dysfunctional or impaired and have lower amounts of GLP1R.In the new research, Shalev's team found that overexpression or too many copies of miR-204 decreased the expression of GLP1R in rat beta cells, and in mouse and human pancreatic islets.Conversely, overexpression of GLP1R means less expression of miR-204 in beta cells and pancreatic islets.

Having high levels of GLP1R helps transfer a signal to beta cells to produce more insulin.Newer diabetes drugs act as agonists, substances that initiate a physiological response to enable GLP1R.This means that higher amount of GLP1R in the body allows use of diabetes medication in a lower dosage to treat the illness, and reduces the side effect from dose dependence.

Using mice models, the researchers cited that removal of miR-2014 enhanced the expression of GLP1R, improved blood sugar control, and increased the production of insulin.The mice were also more responsive to a GLP1R agonist in glucose tolerance test.The findings indicated that reducing miR-204 increases GLP1R which may lead to better treatment for diabetes without risking the patient's health condition to side effects.

"Since miR-204 is expressed primarily in pancreatic beta cells, manipulating its levels allows for preferential upregulation of GLP1R in the beta cell where it helps secrete insulin, rather than in the gastrointestinal system where it can cause nausea and impaired gastric emptying, or in the pancreas, where it can increase the risk for pancreatitis.So by inhibiting miR-204, one could increase the effects of GLP1R agonist drugs on insulin secretion, thereby lowering the necessary dose and avoiding some of the dose-dependent adverse effects," said Dr.Shalev.

Beta Cells of the Pancreas

Beta cells are unique cells found exclusively in the pancreas.Their main purpose is to produce, store, and release insulin.When sugar in the blood rises, beta cells secrete stored insulin and at the same time, increase the amount of insulin.In people with type 1 diabetes, beta cells are attacked or destroyed by the immune system while in people with type 2 diabetes, beta cells are not producing enough insulin to control blood sugar levels.

Aside from producing insulin, beta cells also secrete amylin and the connecting peptide, byproducts of insulin.Amylin controls the rate of glucose entering the bloodstream while c-peptide helps prevent vascular complications, such as neuropathy, by helping repair the muscular layers of the arteries.Together, these chemicals manage the fat and sugar levels in the bloodstream.

Anti-diabetic Medications

For type 1 diabetes, treatment includes insulin intake from drugs, monitoring of blood sugar levels, eating a healthy diet, and regular exercise.Insulin medications are made of different types, such as short-acting, rapid-acting, intermediate-acting, and long-lasting, and your physician will choose the best type for your condition.Insulin can be administered in different drug delivery systems including injections and pumps.Your physician will also determine which kind of delivery system fits your profile.

For type 2 diabetes, the treatment involves the similar lifestyle of recommended for type 1 diabetics, such as eating healthy and regular exercise.Anti-diabetic medications are also prescribed by doctors to help you control your blood sugar level.These medications do not provide the exact method to control diabetes.Some of them are designed to increase sensitivity to insulin to use the hormone efficiently, while others help your body to produce more insulin.Newer medications have different approaches like slowing your digestion to help lower blood sugar levels or prevent the kidneys to reabsorb sugar and flush it out in your urine.Side effects of anti-diabetic drugs include upset stomach, skin rash or itching, weight gain, bloating, tiredness, and metallic taste.

Additional Information

- Diabetes was a direct cause of the 1.5 million deaths in 2012.

- The number of people with diabetes nearly quadrupled since 1980.

- Type 2 diabetes can be preventable while type 1 diabetes risk factors remain unknown; experts are still strategizing on how to prevent it.

- Diabetes can cause numerous complications including heart attack, stroke, and kidney failure.

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