Mitochondrial metabolism
Principal Investigator
Hindrik Mulder, Lund University
Hindrik.Mulder@med.lu.se
Research area description
Our work asks important questions about metabolism in the pancreatic islet. The pancreatic islets, also known as the Islets of Langerhans, harbour several types of endocrine cells that secrete hormones controlling whole body metabolism. The most important cell types is are the beta-cell, which secretes insulin, our major anabolic hormone, and the alpha-cell, which secretes glucagon. Insulin is released in response to a rise in blood glucose levels after a meal, and ensures that the sugar is taken up into peripheral tissues, such as skeletal muscle and fat cells, while glucose production in liver is blocked. Glucagon, on the other hand, ensures that blood glucose is available in between meals. This is accomplished by breakdown of glycogen in liver.
When the control of metabolism by insulin fails, diabetes evolves. Diabetes is the most common endocrine disease and its incidence is increasing globally at an alarming rate. Disruption of beta-cell function and consequently insulin secretion is ultimately the cause of all forms of diabetes.
Traditionally, diabetes has been categorized as Type 1, presenting in childhood/youth, or Type 2, occurring in older individuals. In Type 1 diabetes, destruction of the pancreatic beta-cells by the immune system results in an absolute deficiency of insulin. In Type 2 Diabetes, there likely is a genetically determined inability of the pancreatic beta-cells to secrete sufficient amounts of insulin. The demands on the beta-cells increase when insulin resistance is also prevalent; this frequently occurs in obesity and physical inactivity, but increasing age is another important factor. The limited ability to secrete appropriate amounts of insulin results in hyperglycemia but also other perturbations of metabolism evolve, such as hyperlipidemia. Type 2 Diabetes accounts for the dramatic increase in incidence of the disease.
In recent years large-scale genetic analyses of Type 2 Diabetes have revealed a number of genes, which are associated with the disease. Most of these genes appear to be relevant for islet function. Our work is focussed on understanding how some of these genes mechanistically cause beta-cell dysfunction. On our behalf, this involves a better understanding of metabolism in the pancreatic alpha- and beta-cells. This will potentially resolve why insulin secretion is deficient in Type 2 Diabetes and may provide targets for treatment of the disease.
To reach this goal, our work comprises the following aims:
- Improve analysis of metabolism in islets
- Resolve the role of mitochondrial metabolism in pancreatic beta-cells
- Examine melatonin and its receptors in pancreatic islets
- Understand the link between neurodegeneration and endocrine disorders
- Examine metabolism in pancreatic alpha-cells