Contribution of Glucose
Blood glucose is the primary energy source and is obtained primarily through food consumption. Insulin, a hormone produced by pancreatic beta cells, promotes glucose transport into cells for use as energy. The body either does not produce enough insulin or does not use insulin effectively in type 2 diabetes. More reaches the cells when the blood contains an excess of glucose.
A new study by Dr Elizabeth Haythorne and Professor Frances Ashcroft of the Department of Physiology, Anatomy, and Genetics at the University of Oxford revealed how chronic hyperglycemia causes beta-cell failure.
Glucose Metabolism
The researchers discovered that the products of glucose metabolism, rather than glucose itself, impair the function of insulin-producing beta cells in a series of cell and animal studies. High blood glucose levels stimulate glucose metabolism in the beta cell, resulting in a metabolic bottleneck and upstream metabolite pooling.
These metabolites inhibit the insulin gene, resulting in less insulin production and many other genes involved in metabolism and stimulus-secretion coupling. As a result, the beta cells become glucose-blind and stop secreting insulin in response to changes in blood glucose.
The researchers also discovered that inhibiting glucokinase, an enzyme that regulates the first step in glucose metabolism, could prevent gene changes and maintain gene expression. This could be a promising approach to controlling the beta-cell decline in diabetes.
According to research, glucokinase activators may have a negative effect, and glucokinase inhibitors, counter-intuitively, may be a better strategy for treating T2D. Of course, limiting glucose flux in (Type-2 Diabetes) T2D to that found in non-diabetics – and no further – would be critical. However, more research is needed to determine whether this approach helps treat beta-cell decline in T2D.
