Demonstrated for the first time directly in humans: Insulin action in the brain regulates glucose metabolism

Selective insulin action in certain brain areas improves glucose metabolism throughout the body. This is a finding of a study by scientists at the German Center for Diabetes Research from the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Zentrum München at the University of Tübingen, published in the journal ‘Diabetes’.

In a study led by Dr. Martin Heni and Prof. Andreas Fritsche from Tübingen, researchers administered insulin in the form of a nasal spray to healthy young men. By means of this method, insulin is taken up through the nasal passages and transported directly to the brain. Before and after the intranasal application of insulin, the glucose metabolism and the insulin action in the entire body were measured using the hyperinsulinemic-euglycemic clamp technique. It was found that after the intranasal application of insulin, glucose uptake into the body improved. The researchers also repeated the experiments in obese men, but they showed no improvement in glucose uptake into the cells of the body; this test group showed resistance to insulin action in the brain.

In which brain centers is the metabolism regulated by insulin?
The brains of the study participants were assessed by magnetic resonance imaging before and after the administration of the nasal insulin spray. The assessment showed that the change in the activation of the hypothalamus by insulin correlates to the improvement of the glucose uptake into the body cells. The hypothalamus is known as the control center of the metabolism.

How is the insulin signal in the brain transmitted to the body?
The activity of the autonomic nervous system was measured after the intranasal application of insulin. This activity changed most in those study participants that showed the strongest improvement of glucose uptake into the body cells, thus demonstrating that the autonomic nervous system transmits the insulin signal in the brain to the body.

Importance of the research
For the first time it could be demonstrated in humans that insulin action in the brain improves glucose metabolism. This mechanism probably plays an important role postprandially (after eating), when insulin levels rise to facilitate glucose uptake in the body. The effect could only be shown in lean study participants. By contrast, obese study participants were resistant to insulin in the brain. The study shows that changed reactions in the brain are involved in the development of whole-body insulin resistance, a key factor of type 2 diabetes.

Original publication:
Heni M, Wagner R, Kullmann S, Veit R, Mat-Husin H, Linder K, Benkendorff C, Peter A, Stefan N, Häring HU, Preissl H, Fritsche A. Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes. 2014. doi: 10.2337/db14-0477.
Link to publication