Insulin is a hormone produced by cells in the pancreas called β-cells. Insulin keeps blood sugar levels from getting too high (hyperglycemia) or too low (hypoglycemia). Diabetes is a chronic disease in which the body either doesn’t produce enough insulin (Type 1) or cannot use the insulin it does produce (Type 2). Managing blood sugar levels is important as high blood sugar can cause complications such as kidney disease, eye disease, heart attack, or nerve damage. Diabetes management includes monitoring physical activity, nutrition, weight, stress, and blood pressure. Type 1 diabetes is always treated with insulin, and Type 2 may require insulin and/or other medications. One such group of medications are called sulfonylureas. Sulfonylureas are used to treat Type 2 diabetes as they bypass the normal glucose-sensing mechanism to initiate insulin secretion. As a result, blood-glucose levels lower and the risk of secondary complications decreases. Unfortunately, prolonged treatment eventually exhausts the insulin-producing β-cells leading to a loss of blood sugar regulation. The mechanism by which chronic sulfonylurea treatment affects β-cells is poorly understood.
In their article, Remedi and Nichols injected slow-release pellets with a type of sulfonylurea called glibenclamide into mice. They then monitored the mice’s blood sugar levels. They found that the mice progressively developed diabetes and were unable to secrete insulin. After the drug was washed out, insulin levels rebounded. This study may seem simple, but it tells us that sulfonylureas do not cause irreversible damage or β-cell death, and exhausted β-cells can recover to produce insulin again. This study also utilized normal mice rather than genetically-modified mice, which alleviated concerns about potential defects in pancreas development in mutant mice. Future work should address the precise mechanism of reversible suppression of insulin secretion by sulfonylurea treatment.
Fun fact: In August 1978, Dr. Herbert Boyer produced synthetic insulin using transgenic genetically modified bacteria!
Summary written by: iGEM Team HAFS (South Korea)
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9Chronic Antidiabetic Sulfonylureas In Vivo: Reversible Effects on Mouse Pancreatic β-Cells
