Abstract

More than 400 million people have type 2 diabetes worldwide, highlighting the urgent need for new therapeutics. Over time blood glucose levels leads to blindness, heart disease, and kidney failure. The goal of all diabetes drugs is to reset glucose levels back to normal to avoid these devastating symptoms.  Obesity is the most significant risk factor for developing type 2 diabetes, and therefore strategies to reduce obesity would be idea therapeutics to treat diabetes. Glucose levels are controlled by the natural hormone insulin produced in the pancreas and released after a meal to assist tissues in taking up sugar for energy. The administration of insulin is commonly used to treat diabetes.  The Saghatelian lab discovered a small drug-like molecule called 6bK that prevents the breakdown of insulin by blocking the protein that degrades insulin. Administration of 6bk leads to elevated insulin levels and the lowering of blood glucose levels. These promising results required additional work to determine whether 6bK is a viable therapeutic option for the treatment of diabetes. The goal of this proposal is to test the consequences of long-term 6bk treatment in mice. Specifically, we will examine the effects of 6bK in obese mice and determine whether this drug-like molecule can lower blood glucose and reduce body weight. In addition, we propose to test whether 6bK improves the activity of known anti-diabetic drugs. This project will strengthen the idea that 6bk can treat diabetes and help millions of patients.