Jan W Eriksson

Supervisor ESR5, ESR6

Jan W Eriksson has been a full Professor and Chair of Clinical Diabetes Research at Uppsala University Hospital since September 2013. He has served as a supervisor for 10 PhD students, 15 post-doctoral fellows and a tutor for many (>15) medical and pharmaceutical graduate and undergraduate students doing individual research projects. Jan Eriksson´s research group has a large network of partners – local, national and international- in both Academia and pharmaceutical industry. Jan Eriksson is the Principal Investigator of a clinical and experimental research laboratory in diabetes and metabolism in the Department of Medical Sciences at the Uppsala University with a focus on the following research lines:

1. Group description

Clinical Diabetes and Metabolism

2. Research lines

2.1. Hormonal and metabolic mechanisms in human adipose tissue – importance for the development of type 2 diabetes

The project focuses on metabolic dysregulation in human adipose tissue and its importance for insulin resistance, type 2 diabetes and their complications.

Specific aims are:

  • Exploration of novel mechanisms and markers in adipose tissue involved in the development of insulin resistance and type 2 diabetes.
  • Investigation of cross-talk between adipose tissue and other tissues in the body, like the central nervous system and gut, in the context of obesity, insulin resistance and type 2 diabetes.

2.2. Effects of gastric by-pass (GBP) surgery on glucose and lipid metabolism

The project is run in collaboration with the Dept of Surgery at Uppsala University, and focuses on the profound changes seen in glucose and lipid metabolism following bariatric surgery.

Specific aims are:

  • To investigate metabolic effects of GBP in comparison to similar weight loss achieved with very low-calorie diet (VLCD) on glucose and fatty acid turnover as well as insulin sensitivity in specific tissues and functional assessments of the insulin-producing beta cells.
  • To address mechanisms explaining the remission of diabetes that is often seen following GBP.
  • To investigate the metabolic and hormonal mechanisms involved on postprandial hypoglycemia, a complication that affects some post-GBP patients.

2.3. Pharmacology of human adipose tissue in metabolic disease

Many therapeutic agents affect glucose tolerance and can predispose to diabetes, especially when pre-existing factors are present. These drugs may act by increasing insulin resistance, by affecting insulin secretion or both. Examples include glucocorticoids, immunosuppressive agents and antipsychotic drugs. Our group aims to identify novel mechanisms for insulin resistance induced by these drugs in insulin sensitive cells, in particular human adipocytes, by exploring pharmacologic manipulation, in vitro and in vivo, leading to insulin resistance.

Specific aims are:

  • Identify novel mechanisms associated with glucocorticoids induced-insulin resistance
  • Explore the role of FKBP5 and CNR1, two of the major proteins up-regulated by glucocorticoids and associated with insulin resistance, in the glucocorticoid-induced insulin resistance.
  • Explore the role of lipocalin 2 in glucocorticoid-induced insulin resistance in human adipose tissue in pre-menopausal females
  • Explore the underlying mechanisms by which antipsychotic drugs contribute to insulin resistance, dyslipidemia and diabetes.

2.4. Studies of clinical and metabolic effects of novel medicines

We perform several studies exploring the clinical and metabolic effects of novel antidiabetic drugs, like the SGLT2 inhibitors. These studies include exploratory clinical trials for proof-of-concept as well as mechanistic human studies. Our investigations are also combined with PET/MRI technology for detailed measurements of energy metabolism in specific organs and registry-based epidemiological studies for clinical outcomes.

Specific aims are:

  • Effects on energy balance and obesity, on fatty liver disease and endocrine effects related to gut and pancreatic islets in particular.
  • Effects on cardiovascular and other organ complications and mortality as well as health economy are evaluated.

3. TREATMENT project

  • ESR5

    ESR5 will study the effects of the antipsychotic drugs on human adipose tissue glucose and lipid metabolism in order to understand the impact of antipsychotics in human adipocyte glucose metabolism, insulin signaling and lipid handling. Specific aims would be: i) Investigate the effects on glucose uptake (GLUT4 translocation) and its interactions with insulin signaling (IR, IRS1/2, Akt). ii) To elucidate the effects on lipolysis (PKA, HSL, perilipin), lipid storage (TG synthesis) and the expression of lipid metabolism regulatory genes (fatty acid synthesis and oxidation. The ESR will analyze differences in the insulin-stimulated glucose uptake, insulin signaling and lipid handling that may contribute to the development of insulin resistance following antipsychotic treatment. These may contribute to lipid deposition in other organs, such as liver and muscle, leading to dyslipidemia. These studies will provide biomarkers on drug induced adipose tissue insulin resistance.

  • ESR6

    ESR6 will analyze drug induced low-grade chronic inflammation in human adipocytes and cytokine’s effects on adipocytes and other tissues in order to investigate effects of antipsychotic drugs on adipose tissue hormones, adipokines and chemiokines, inflammatory markers, or other factors of potential importance for the development of type 2 diabetes and obesity. Following drug treatment, the ESR will evaluate changes in inflammatory factors (lipid species such as eicosanoids, leukotrienes) and cytokines (TNFα, IL6, IL1β) in adipose tissue contributing to low-grade systemic inflammation, macrophage M2-M1 polarization, whole body insulin resistance and liver steatosis. Furthermore, when comparing samples from healthy and type 2 diabetes subjects, the ESR will analyze putative differences in the drug effects on the inflammatory milieu.

4. Group members

  • Abalo, Xesus, Senior researcher
  • Abrahamsson, Niclas – Physician
Almström, Carola – Nurse team leader
Boersma, Gretha – Senior researcher
  • Ehrenborg, Anna – Research nurse
  • Eriksson, Jan – Professor & Senior Consultant Physician
  • Gelotte, Monika – Research nurse
  • Hall, Jan – Biomedical analyst
  • Kamble, Prasad – PhD student
  • Karlsson, Anders – Professor
  • Katsogiannos, Petros – Assistant physician & PhD student
  • Lundkvist, Per – Assistant physician & PhD student
  • Löfving, Sofia – Project coordinator
  • Pereira, Maria João – Post doctoral researcher
  • Sidibeh, Cherno – PhD student
  • Svensson, Maria Eriksson – Adjunct senior lecturer

5. Links