It’s incredibly exciting. The cells have an intrinsic rhythm which means hormone secretion occurs in a pulsatile manner. But despite of the fact that beta and alpha cells are positioned next to each other in the islets, they move to opposite beats.
The pancreas contains around a million islets that must work together in rhythm in order for the hormones to pulsate through the bloodstream. An early sign of the development of type 2 diabetes is that the rhythm is off”, he explains.
The attraction of research
Anders Tengholm is head of a research group at the Department of Medical Cell Biology at Uppsala Biomedical Center and is part of EXODIAB, which is a collaboration between the universities in Uppsala and Lund. His fascination with science is obvious. He was well on his way to becoming an MD but decided to post-pone his studies at a late stage. ”The field of research was too tempting”, he explains. What was meant to be a short break from his medical studies became a permanent choice.
Shortage and surplus
Type 2 diabetes is characterised by a shortage of insulin, which means that the body’s cells are unable to utilise nutrients in food. Instead, sugars accumulate in the bloodstream. In many cases there is a concurrent surplus of glucagon, which is normally secreted during fasting. Both these disruptions contribute to the high blood glucose levels that characterise diabetes.
”My research focus is on the cellular level”, says Anders Tengholm, and explains how it is possible to follow the signalling and secretion activity in live cells. Anders Tengholm and his research group were the first to present several new methods for studying the rhythm in isolated beta and alpha cells.
”These methods are essential if we want to understand how the endogenous rhythm arises. We can follow different processes in one single cell, second by second, and thus map the interaction between different signals and the regulation of hormone secretion”, he summarises.
Five minutes intervals
The regulation of blood glucose levels is an intricate and fine-tuned hormonal balancing act. ”Rising blood glucose levels trigger a signalling chain which causes coordinated oscillations on the levels of several important carrier substances in the beta cells. In healthy individuals this leads to pulsatile insulin secretion. The pulses occur at intervals of around five minutes and has the largest impact on the liver, which is the organ that the insulin reaches first”, says Anders Tengholm.
Less insulin required
”The pulses mean that less insulin is required in order to get the same blood glucose-lowering effect. If liver cells are exposed to insulin continuously, the insulin receptors disappear from the cell surface. The pulsations prevent the number of insulin receptors from decreasing and the liver cells are therefore always prepared to respond appropriately to insulin. Pulsations are also present in the bloodstream heading to other organs, such as muscles and adipose tissue, but here they are not as pronounced and are of less significance”, explains Anders Tengholm.
Taking turns to the opposite beat
The alpha cell secretion of glucagon occurs to the opposite beat, and alternately with insulin. ”This is logical, as the hormones have contrasting functions, but we still don’t know how the rhythm in the alpha cells arises”, says Anders Tengholm. Following a single cell’s activity requires sophisticated instruments. The diameter of a beta cell is between 10 and 15 micrometres. Anders Tengholm and his colleagues can depict what happens within one ten-thousandth of a millimetre from the cell membrane where many of the processes that control hormonal secretion take place.
Technically driven development
”Developments are driven by technical advances, both when it comes to depiction methods and the molecular tools we use to visualise different cellular processes. It was thanks to the techniques that enable the analysis of calcium ions in single cells that colleagues here in Uppsala discovered the endogenous rhythm of the beta cell over 20 years ago. Today, scientists know a fair amount about calcium signalling, but it wasn’t until say five to ten years ago that we were able to start measuring a number of other important carrier substances. A very important universal tool we use is a fluorescent jellyfish protein by means of which many different molecules can be traced”, explains Anders Tengholm.
Healthy cells point the way
To date, the research group’s focus has been on mapping normal insulin secretion from healthy cells and the analyses have primarily been carried out on cells from mice or so called ‘cell lines’. Recently, the group has also begun to study human beta cells from deceased donors. ”In order for us to be able to correct dysfunctions in people with type 2 diabetes we must first understand how hormone secretion works in healthy individuals. It has long been known that in diabetes, the rhythm of hormone secretion is disrupted, but it’s too early to say what causes this”, says Anders Tengholm.
Not just research
Despite long days at the office, there is more to life for Anders Tengholm than just work. He has been fascinated by nature since he was very young and at school, science and biology were obvious choices. ”Being a scientist is very stimulating and exciting but there are many other things that bring happiness to my life. My wife and our two children are very important to me. Birds and music are two other big interests since way back,” he says.
For some reason, bird-watchers seem heavily overrepresented amongst scientists so this interest is perhaps neither surprising nor especially original. ”Perhaps it has something to do with a researcher’s endeavour to structure and systematise the world around us. It’s interesting to identify what you hear and see when you’re in nature, and birds are comparatively easy to understand. Besides, they’re beautiful creatures with a fascinating way of life”, says Anders Tengholm.
Authentic big band jazz
His teenaged sons share the family’s interest in nature, but if they will become scientists as well remains to be seen. Another interest, probably more uncommon among researchers, is jazz. Again, the boys share their father’s interest, one of them plays the contrabass and the other, like his father, plays the trumpet. ”And, I play in the Canal Street Syncopators. We play authentic big band jazz from the 20’s and 30’s. Playing is extremely relaxing. You get to use parts of yourself that you wouldn’t use otherwise”, says Anders Tengholm.
Text: Tord Ajanki/Camilla Franks
Picture: Dragan Prvulovic, MalmöBild AB (Anders Tengholm)