Insulin is an indispensable treatment for type 1 and type 2 diabetes for about 8.4 million Americans according to the American Diabetes Association. However, too much insulin can be lethal, and the mechanism that protects us from excessive insulin in the body has remained a mystery. A new study published in Cell Metabolism by University of California San Diego scientists gives insight into this protective mechanism. The study describes “the body’s natural defense or safety valve” against insulin shock- a metabolic enzyme called fructose-1,6-bisphosphate phosphatase or FBP1, which controls gluconeogenesis- the process the liver uses to synthesize glucose and maintain a steady supply of glucose in the bloodstream. The study found that FBP1 has a second non-enzymatic but critical function in inhibiting the protein kinase AKT, the primary conduit of insulin activity. FBP1 keeps AKT in check and guards against insulin hyper-responsiveness, hypoglycemic shock, and acute fatty liver disease. A peptide derived from FBP1, nicknamed E7, could reverse insulin resistance and restore normal glycemic control in mice that have been rendered insulin-resistant, a highly common pre-diabetic condition due to prolonged consumption of high-fat diets. The researchers hope to develop E7 as a clinically useful alternative to insulin as it is unlikely to cause insulin shock.
