Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Hjelt Foundations grant holders 2020

Karin Stenkula, Emily Sonestedt and Sebastian Kalamajski have received grants from the The Bo and Kerstin Hjelt Diabetes Foundation. Read about their research projects here.

Karin Stenkula
Karin Stenkula, Lund University Diabetes Centre:

EHD2: a novel candidate essential for lipid transport and overall glucose homeostasis

Obesity is one of the main risk factors behind type 2 diabetes and cardiovascular diseases. Both obesity and type 2 diabetes are characterized by an insulin resistance, which means that even though insulin is released into the blood, it does not stimulate uptake of fat and glucose into the cells. This results in elevated blood glucose levels, which can develop into type 2 diabetes. Still, it is not known how an increased fat tissue mass is linked with onset of these diseases. 
Recently, the protein EHD2 was shown to promote both insulin sensitivity and fat cell function. In the present proposal, we hypothesize that EHD2 is central for regulating uptake of both glucose and fat from the blood. To test our hypothesis, we will apply a variety of cell biology- and microscopy techniques to monitor cellular insulin response, and nutritional uptake. To specifically address the role of EHD2 for these processes, we will analyze fat cells isolated from both normal, wild-type mice and a recently established mouse model lacking EHD2.  
Possibly, knowledge of how EHD2 contributes to maintain intact fat cell function can result in new strategies to improve insulin sensitivity and lipid storage capacity in fat cells. This will be useful to both prevent and improve adipocyte dysfunction, with beneficial effects on whole-body glucose homeostasis.

More about Karin Stenkula in Lucris


Emily Sonestedt, Lund University Diabetes Centre:

Emily Sonestedt
Emily Sonestedt Bild: Björn Martinsson

Effect of having low or high salivary amylase copy number on postprandial response to different starch doses

Genetic factors can influence our ability to digest carbohydrates. The gene encoding for salivary α-amylase, AMY1, has gathered attention in recent years due to the extensive copy number variation (when sections of the genome are repeated in various numbers in different individuals). Individuals with few copies of the AMY1 gene have lower levels of salivary amylase and may have difficulty digesting starch into glucose. We have in a study comprising 19 subjects found a higher postprandial (after eating) glycemia in those with high AMY1 copy number compared to those with low copy number. We now intend to examine the postprandial response to two different starch doses in 60 individuals with low or high AMY1 copy number. Including outcomes such as breath analysis, microbiota and metabolites such as sugars, lipids, amino and organic acids, would give us a more detailed insight into the effect of AMY1 copy number on starch digestion and glucose metabolism. Participants will be recruited from the Malmö Offspring Study by genotype-based recall. We will also examine whether AMY1 copy number is associated with microbiota composition and metabolites among approximately 1500 individuals from the cohort to further understand the metabolic profile of those with low and high copy number. Because high postprandial glycemia is a risk factor for type 2 diabetes, this research project will hopefully contribute to more personalized prevention strategies in which glucose intolerance could be reduced by recommending specific starch intakes depending on the AMY1 copy number. 

More about Emily Sonestedt in Lucris

Sebastian Kalamajski
Sebastian Kalamajski
Sebastian Kalamajski, Lund University Diabetes Centre:

"Creating A Human Disease-In-A-Dish Model Of Diabetes By Genetically Engineering iPSCs Using CRISPR/Cas9"

Type 2 diabetes is associated with several physiological shortcomings in our organism, one of which is the inability of our tissues to respond to insulin. Also, the insulin-producing beta cells in pancreas can lose their insulin secretion capacity, which further complicates the matter, and contributes to elevated blood glucose. It is now known that a few hundred common human genetic variants may influence the capacity of beta cells to produce and secrete insulin. However, in many cases we lack a definitive proof that these genetic variants directly contribute to, and not merely associate with diabetes.  To solve this puzzle, in our research we intend to combine the latest advances in genomic editing and in human stem cell technology to uncover how common human genetic variation can jeopardize an efficient insulin production or secretion in pancreatic beta cells.
One of the hypotheses we intend to test is that a specific human genetic variation influences how the beta cell responds to melatonin. Melatonin is a sleep-related hormone that should shut down insulin secretion during fasting, i.e. when we sleep and not want our blood glucose to decrease too much. On the other hand, too much shutdown of insulin secretion by melatonin could create excessively low blood insulin levels when we need it, perhaps after an evening meal. In previous studies scientists have identified genetic variation in a gene called MTNR1B that appears to determine the levels of insulin secretion in the presence of melatonin. The response of the beta cell to melatonin, depending on what type of genetic variant in the MTNR1B gene it carries, may therefore be a potential contributing factor to diabetes.
To test the above hypothesis we need to establish cell lines that have exactly the same genomic sequence, except for the one variation in the MTNR1B gene. We intend to accomplish this using genomic editing technology called CRISPR/Cas9, which we’ll utilize on human stem cells donated by people that carry the MTNR1B gene variant often found in type 2 diabetes patients. We will attempt to switch the cells’ genetic code to one that is associated with lower risk of diabetes, and then evaluate how these stem cells develop into mature insulin-producing beta cells, and how these cells’ insulin secretion is affected by melatonin. Using this strategy we will be able to dissect the contribution of particular genetic variants to the central role of beta cells, which is providing our tissues with insulin. 
Our study also carries a secondary aim – once the above-described technologies become established we will be able to study the effects of other human genetic variants on the biology of beta cells in a much more reliable way than has so far been possible. We hope that combining the latest genomic editing with stem cell technologies will result in new knowledge of type 2 diabetes genetics, and create new perspectives on personalized diabetes medicine.

More about Sebastian Kalamajski in Lucris

The foundation also funds research from the University of Geneva:


Rodolph Dusaulcy, University of Geneva:

Precision diabetes in paediatrics:
Screening of molecular and functional effects of new gene variants

Diabetes is defined by chronic hyperglycemia which may lead to dangerous complications. Type 2 diabetes and type 1 diabetes are the best known forms. Type 2 is often associated with obesity, while type 1 is an autoimmune disease where the immune system destroys the insulin-producing pancreatic beta cells. The form of diabetes studied here is called “monogenic”, and is caused by a mutation in a single gene. These monogenic diabetes forms represent up to 4% of diabetes cases in pediatric populations and are characterized by alteration of beta cell function and or beta cell mass reduction.
Our objective is to identify and validate new genes and mutations responsible for monogenic diabetes. We previously sequenced over 400 genes potentially implicated in diabetes in a population of children with a suspicion of monogenic diabetes. We thereby identified a series of sequence variants in novel and known genes that constitute potential new monogenic diabetes genes and variants.
We hypothesize that these variants may reduce the capability of beta cells to adapt and resist to stressors such as fat and sugar excess or inflammatory mediators. We propose to study in vitro, in human and mouse beta cells, the specific impact of the identified genes and variants. On one hand, we will silence the expression of target genes and, on the other hand, reproduce in vitro the variants observed in diabetic children. To do that, we plan to use a new technology, called the Crispr/Cas9 system, to reproduce the sequence variants in beta cells. Then, we will study the consequences of these gene defects at molecular and functional level by assessing the impact on insulin production and release, cell proliferation and survival. 
We believe that this project will be helpful for diabetic children and will allow a better understanding of disease development, adaptation and personalization of the treatments as well as the potential development of new therapeutic strategies.


Daniel Oropeza, University of Geneva:

"Characterization of metabolism and its regulation of gene expression in primary human pancreatic alpha and beta cells"

Type 2 diabetes is a complex multifactorial disease in which a pathological combination of metabolic and genetic factors severely affects the normally exquisite control of blood glucose levels performed by our metabolic organs. There are two highly specialized endocrine cells in the pancreas that secrete hormones that can abruptly change blood glucose levels: the insulin-secreting beta cells and the glucagon-secreting alpha cells. These perplexing cells have diametrically opposed functions: insulin is secreted at high blood glucose levels to promote efficient glucose absorption into our organs while glucagon is secreted at low blood glucose levels to trigger release of glucose from our organs. The delicate balance in secretion of insulin and glucagon forms the basis through which our bodies maintain healthy blood glucose levels at all times. 
Various cellular mechanisms control the function of alpha and beta cells, including the fine-tuning of hormone production and secretion in response to subtle changes in the environment, which are sensed through the metabolism of the nutrients circulating in our blood. Unfortunately, for the most part, these basic mechanisms are still poorly understood because of the difficulty in analyzing human alpha and beta cells due to their anatomical configuration and low abundance in our body. In particular, there is very little information regarding how do human alpha cells metabolize sugars, lipids and amino acids. Recently, in our laboratory we have developed novel methods that allow us to efficiently isolate numerous human alpha and beta cells and perform many different types of experiments and analyses. Using these new techniques, we will perform a comprehensive characterization of the metabolism of human beta and alpha cells to understand how they react to the changing metabolic status that is a hallmark of type 2 diabetes.
In addition, we believe that the different ways alpha and beta cells metabolize nutrients to generate new metabolic molecules is intimately linked to how they control the activation or inhibition of specific genes that help to define the key differences between these two cell types. Like for example the decision to whether produce glucagon or insulin as a hormone. Thus, to better understand this process, we will also study how does the metabolism of alpha and beta cells impact the activity of genes that maintain their key diametrically-opposed cellular and physiological differences. 
The results from our experiments will generate important and basic information about the key role of metabolism in human pancreatic alpha and beta cell biology, which will be highly relevant to understand how Type 2 Diabetes develops given the strong link between the disease and metabolic dysregulation.