A Letter from Niels Juel Christensen

A Letter from Niels Juel Christensen, MD, to the APS Distinguished Physiologists, March 2019

“Thank you for your kind letter and greetings for my birthday. I feel highly honored to write this letter sharing some of my life experiences with other members in our society.

When I finished my studies to become a doctor in 1964, I wanted to start a scientific work. I therefore asked one of my teachers Professor Knud Lundbæk, whether he would help me through a Ph.d. study. Knud Lundbæk was well-known for his studies of diabetic nerve and vascular disease and head of a large endocrine department with a laboratory affiliated with Aarhus University.

After completing my Ph.d. study I wanted to continue researching. I was aware it was necessary to define my own research area. Something unexpected could appear, and it could be important to take a chance, and examine it more closely.

During work with my Ph.d., I had observed that the spontaneous variation in resting blood flow in the feet was absent or considerable reduced in diabetic patients with autonomic neuropathy. I was therefore interested in investigating the sympathetic nervous system and catecholamines. In one of my studies, I randomly found that insulin administration increased the sympathetic activity as measured by plasma norpinephrine. This response was unrelated to the blood glucose concentration (Christensen; 1974). We also observed that insulin increased the capillary permeability of albumin and the number of microparticles in capillary endothelial cells from muscle tissue (Gundersen & Christensen; 1977). These changes are a least in part due to an increase in capillary blood flow in muscles. We also examined the permeability of the kidney. Oral administration of glucose resulted in a short, but significant increase in albumin secretion in normal subjects but not in diabetic patients, unless insulin was injected  (Hegedus et al.; 1980). The kidney was clearly sensitive to insulin.

The above-mentioned changes in capillary permeability and the increased permeability of the kidney were thus not caused by changes in blood glucose and are now referred to as non-metabolic effects of insulin. We did not understand how insulin worked on the kidney, but Coward et al. (2005) and Piwkowska et al. (2013) found that insulin increased glomerular permeability via an effect on podocytes. Eventually, the effect of insulin on the kidneys was clarified. Madhusudhan et al. (2015) demonstrated that lack of insulin signaling causes damage to the endoplasmic reticulum in the podocytes. (References to the above can be found in DOI: 10.15406/mojddt.2017.01.00009).

In 1977 I moved to Copenhagen to work at the new university hospital in Herlev. Professor Laurids Korsgaard Christensen was head of the endocrine department and well known for his many studies of thyroid diseases. As he retired, I took over his position as chief and was appointed professor at the University of Copenhagen.

Around 2000, we began to work with molecular biology. One of my skilled staff in the laboratory developed a method for measuring RNA that included HPLC, so that we could measure not only the amplified amount of DNA after reverse transcription but also the size of the fragment. We found an unknown long non-coding RNA sequence named Heg lnc RNA.  Heg is derived from the Nucks gene, which plays a crucial role in transcription. The concentration of Heg in mononuclear cells was negatively correlated to amounts of TSH receptor autoantibodies in the blood of patients with Graves´ disease. In normal subjects and in treated patients, Heg was negatively correlated to CD14 mRNA in mononuclear cells. There was no difference in the effect of endogenous and exogenous Heg on CD14 mRNA . It is possible that the amount of Heg lnc RNA determines how much autoantibody, there can be produced via an effect on CD14 or Nucks without affecting the specificity of the autoantibody. It would therefore be of interest to examine Heg in patients with type 1 diabetes. (For references see DOI: 10.15406/mojddt.2018.02.00040).

I worked together with other groups of researchers to elucidate the significance of the sympathetic nervous system and of dopamine.  We examined the regulation of sympathetic nervous activity in aging and obesity, in patients with autonomic neuropathy and tetraplegics, at exercise, and in astronauts at the international space station in collaboration with Roscosmos, ESA and NASA. Furthermore, we made various studies of the kinetics of catecholamines. We found, among other things, that the sympathetic activity was high among astronauts in space despite the small effect of gravity.

The above comments refer primarily to research done at the universities. If you want to  research in the industry, the conditions are different. Here it is important that you can work together with other researches on the planned project. There is a significant difference working in a small team and a big team described in more detail by the so-called disruptiveness index.

Be aware of and at an early state that articles to be published must have quality, so they can be published in a journal with a high impact factor. It is also important to attend international meetings and show the new results and to discuss their significance with other researchers.

Science is one of the areas where success plays a major role with new and important findings. Therefore, there is much envy and slander of the one who have made an interesting discovery. The best thing to do is ignore these negative comments.

I had a lot to do because, in addition to the research work, I was also responsible for the medical department and treatment of patients. I liked to teach the medical students and was happy when I was awarded a prize as the best teacher of the year.

(A short discussion of some of our results can be seen in my APS Living History video).”