New treatments for metabolic diseases, such as type 2 diabetes, could emerge from a study of how a single enzyme controls the growth of the pancreatic cells that produce insulin.
Researchers at Pennington Biomedical Research Center will investigate how the enzyme SGK1 regulates beta-cell mass when the body signals that more insulin is needed. The lab will also examine the mechanisms behind increases in the number of beta cells and changes in insulin production during calorie overload, obesity and insulin resistance.
Collectively, the results of the research will expand on our knowledge of beta-cell growth mechanisms and how these processes influence insulin release. Ideally, we hope that this work provides insights leading to new medications that could assist with diagnosing and treating metabolic diseases. This treatment avenue may one day be used to treat or prevent type 2 diabetes."
Jason Collier, PhD, Associate Professor and Director, Islet Biology and Inflammation Laboratory, Pennington Biomedical
The National Institute of Diabetes and Digestive and Kidney Diseases awarded Dr. Collier a five-year, $1.8 million grant to fund the research.
The study will test the theory that restricting the SGK1 enzyme regulates the secretion of insulin and limits the growth of the cells that produce the hormone, which controls blood-sugar levels.
"Under normal conditions, there is a certain number of beta cells in the pancreas. During the early stages of obesity and insulin resistance, the number of beta cells increases, and additional insulin is secreted," Dr. Collier said.
"However, does the increase in number of cells lead some to become dysfunctional so they no longer make enough insulin to prevent high blood sugar levels? This is something we are trying to understand in more detail."
Collier's previous research on inflammatory signaling pathways eventually revealed that levels of SGK1 rapidly increase and are also altered by exposure to sugar.
The scientists wanted to find out if limiting SGK1 in beta cells stopped them from growing when mice ate too much and began to develop insulin resistance. The scientists genetically modified the mice to keep them from producing SGK1.
"Although the mice ate a high-fat diet, the number of beta cells didn't increase as much as they normally would. Importantly, we were surprised to find that the mice actually did a better job of processing sugar," Dr. Collier said. Research is ongoing to unravel these important processes occurring during obesity and insulin resistance.