Sara Linse

Sara Linse says: “Type-2 diabetes affects over 400 million people world-wide and is linked to aberrant behavior of the hormone IAPP. IAPP is produced, stored and released together with insulin, which is needed for our sugar metabolism. In most cases of type-2 diabetes, IAPP is found in aggregated form. This causes death of the insulin-producing cells. Current efforts to develop inhibitors against IAPP aggregation are spent without knowledge of the underlying mechanism. This is where this project comes in. We will first solve the mechanism in term of which steps happen and which of these steps cause death of insulin-producing cells. Inhibitor design will then target exactly these steps to limit cell death. This is important as targeting the wrong steps can even lead to increased cell death. We will optimize all parts of the experiments needed to find the mechanism in the relevant biological fluid, and the action of each potential inhibitor under conditions relevant to the situation in the human body.”

Claes Ohlsson

Claes Ohlsson says: “With increasing age of the population, we are facing a substantial increase in bone fragility fractures, which account for considerable disease burden and costs. Therefore we aim to improve the prevention, diagnosis and treatment of osteoporosis and related fractures. We will identify human genetic signals for a variety of specific fracture-related phenotypes and translate these to novel mechanisms regulating fracture risk. The clinical usefulness of the most promising genetic markers will be evaluated in the fracture risk prediction tool FRAX® that, according to national guidelines in Sweden and many other countries, should be used to aid in fracture risk prediction and thereby in the selection of individuals who would benefit most from osteoporosis treatment. Our vision is to develop fracture type-specific diagnostic tools and treatments facilitating a more personalized anti-fracture therapy.”

Kim Rewitz

Kim Rewitz says: “The twin epidemics of diabetes and obesity are major, fast-growing global health challenges. Some of the most promising and innovative approaches to treat these conditions involve manipulating hormonal signals from the gastrointestinal tract. The gut talks to the brain and other organs by releasing hormones into the blood that relay how hungry we are, what we should or should not eat, and whether the body should store energy or burn it. Although some important gut hormones have been discovered, over 2,000 proteins with potential hormonal function exist, representing a significant unexploited resource for the discovery of new therapies against metabolic disorders. The aim of this project is to systematically identify the hormones used by the gut to communicate with the brain and other tissues to regulate appetite and metabolism. Identifying gut hormones that regulate hunger and energy storage may provide new treatments for diabetes and obesity.”

Mattias Carlstrom

Metabolic disorders including type 2 diabetes (T2D) have reached epidemic levels in the industrialized world and is closely coupled with overweight and obesity. It is well known that a diet rich in vegetables has favorable cardiometabolic effects, however, the protective component(s) in such diet remain unclear.

Mattias Carlstrom says: “We have demonstrated that supplementation with inorganic nitrate, which is highly abundant in green leafy vegetables, has favorable effects on cardiovascular and metabolic functions”. The mechanisms are linked to increased nitric oxide production and reduction of oxidative stress. This translational project explores the therapeutic potential, and underlying mechanisms, of dietary nitrate treatment in T2D and associated adverse complications. Results from this proposal may lay a foundation for therapeutic use of nitrate alone or in combination with antidiabetic drugs in T2D and may also lead to novel and specific dietary approaches to prevent the disease.”

Jorge Ruas

Jorge Ruas explains: “Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. It is estimated to affect up to one third of the adult population in industrialized countries and 70-80% of obese patients with diabetes. Over one third of these patients progress into the most severe disease stage, nonalcoholic steatohepatitis (NASH). NASH dramatically impairs liver function and is a major risk factor for cirrhosis, hepatocellular carcinoma, and cardiovascular disease. There are no approved pharmacological treatments for NASH and drug development is challenging since the mechanisms underlying its pathogenesis are not understood. There are no biomarkers to diagnose and monitor NAFLD/NASH progression. We have identified a protein with previously unknown function (TRAIN) and discovered that it is a major driver of inflammation and fibrogenesis. With this project we aim to understand how TRAIN leads to NALFD/NASH, to identify disease biomarkers and to develop novel therapies for NAFLD/NASH.”

Tine Willum Hansen

Tine Willum Hansen says: “The purpose of this study is to identify patients with type 2 diabetes at high risk of developing cardiovascular disease and to get a better understanding of the coexistence and interplay between diabetic kidney disease and severity of cardiovascular disease. To obtain this we will enroll 900 patients for a cardiac positron emission tomography (PET) scan. This is an imaging test that enable the calculation of 1) the ability to increase blood flow in the heart during stress; 2) the calcification of the large vessels in the heart; and 3) the pump function of the heart. After 5 years we will perform register-based follow-up and this will allow us to investigate the link between these three important aspects of the function of the heart and development of cardiovascular disease. The deeply characterization of structural and functional changes in the vessels of the heart will be done in two sub studies.”

Olof Idevall-Hagren

Olof Idevall-Hagren says: ”Most cells in the human body are equipped with a primary cilium. This small protrusion function as an antenna that senses changes in the environment and transmit this to the cell body. Defects in primary cilia is the underlying cause of ciliophaties, a group of diseases characterized by diabetes-like symptoms. If there are direct connections between cilia function and diabetes is not known. We have developed tools that enable visualization of activity within primary cilia of insulin-secreting cells and found that these structures are engaged under conditions that modulate insulin secretion. Olof Idevall Hagren will now use these techniques together with methods that suppress or amplify this activity and determine the importance of primary cilia for insulin production and secretion. Our hypothesis is that these antennae coordinate different responses, e.g. insulin secretion, between cells and that defects in cilia function will have a negative impact on these responses and contribute to diabetes.”

Nicolai Wewer Albrechtsen

In this project Nicolai Albrechtsen aim to understand how the human liver ‘works’ when we eat and which biochemical systems within the liver that are impaired in obese individuals and patients with liver diseases. By bridging an advanced clinical setup in humans to state-of-the-art biochemical techniques such as mass-spectrometry and machine learning the goal is to provide the first ‘postprandial human liver atlas’. Evaluating liver profiles of healthy compared to those with liver disease may guide us to a new understanding of how the human liver works and thereby also aid in the identification of new drug targets for liver diseases.

Nicolai Albrechtsen says: “Overload of nutrients and sedentary life predisposes to obesity and liver diseases. Every time we eat, thousands of biochemical processes are activated in order to help our body digest carbohydrates, proteins and fat. The liver is of particular importance for such as it filters and regulates the amount and type of nutrients that reaches our organs”.

Jakob G. Knudsen

Jakob G. Knudsen says: “Type 2 diabetes (T2D) affects more than 400 million people worldwide. Despite great efforts, we have so far been unable to curb the increasing prevalence. While insulin resistance and lack of insulin secretion seems to be the major cause of T2D, it has become clear that the hormone glucagon also plays a critical role. Glucagon is normally secreted to increase plasma glucose levels during fasting but in T2D, glucagon suddenly appears at higher plasma glucose levels and causes hyperglycemia. In this project, Jakob Knudsen will advance single cell resolution microscopy and genetically modify models to determine how α-cell metabolism and glucagon secretion changes in response to metabolic challenges. this way we can explore the mechanisms underlying glucagon secretion in T2D. The understanding of α­-cell metabolism and the basic mechanism of glucagon secretion will not only benefit diabetes research, but also lead to new possible treatments for T2D.”

Morten Frost Nielsen

Morten Frost Nielsen says: “Bone is an active tissue that is remodelled by resorption and formation of bone throughout life. Imbalanced bone remodelling may impair bone and increase fracture risk, e.g. osteoporosis and type 2 diabetes (T2D). Glucagon like peptide-1 (GLP1), a gut-secreted hormone, promotes insulin secretion when food is consumed and improves bone formation in animal studies. The hypothesis of Morten Frost and his group is that GLP1 acts as a nutrient sensor that signals availability of nutrients for bone remodelling. This project aims to determine the effects of GLP1 on bone formation, mass and strength by investigating the effects of treatment with GLP1 and GLP1-like drugs, currently used to treat T2D, on bone cells and bone in healthy individuals and T2D patients with low bone mass. If GLP1 and GLP1-like drugs are beneficial to bone in humans, this investigation will help repurposing GLP1-like drugs as a novel treatment of patients with conditions associated with increased fracture risk including osteoporosis and T2D.”