Integrative physiology – Juleen Zierath and Anna Krook

The overall aim of the research in integrative physiology is to discover and validate targets important in metabolic disease. A key focus is glucose homeostasis and Type 2 diabetes mellitus, and skeletal muscle insulin sensitivity.

Group of researcher standing together

Our Research

The Integrative Physiology research group focuses on mechanisms underlying metabolic disorders with particular, but not exclusive, focus on insulin resistance in skeletal muscle.

Using novel methodology developed in the group to incubate and analyse human skeletal muscle samples ex-vivo, we were the first to demonstrate defects in insulin stimulation of intracellular signalling molecules in patients with insulin resistant type 2 diabetes mellitus.

Clinical investigations in, parallel with primary human skeletal muscle cultures, where skeletal muscle cells are grown in vitro from patient biopsies, and model organisms are used to approach metabolic disease from a multidisciplinary angle in order to address gene and protein regulation, cell physiology and whole-body metabolism.

Implications

Diabetes is a life-long condition. If left untreated, diabetes can lead to severe medical complications, which include heart disease, stroke, kidney disease, blindness, nerve damage, and severe infections leading to gangrene and foot and leg amputations. Maintaining glucose homeostasis may help prevent these complications.

By identifying the molecular mechanisms controlling insulin-sensitivity it will be possible to develop pharmacological and physiological (exercise and diet) intervention strategies aimed to improve glucose homeostasis. However, diabetes is a heterogeneous metabolic disorder, consequently, a multitude of intervention strategies need to be applied to achieve good glucose control.

The long-term goal is to identify and characterize new molecular targets that control glucose uptake and metabolism in skeletal muscle. Intervention at the level of these targets may control and prevent insulin resistance in Type 2 diabetes.

a big group of people in a lab
VO2 Max testing lab

Current Projects

Skeletal muscle response to exercise interventions

Exercise increases skeletal muscle and whole-body insulin-sensitivity, and the effects of exercise and muscle contraction is a key area of investigation, as are effects of skeletal muscle immobility. Understanding key molecular events activated by exercise can identify novel targets for therapeutic interventions.

Understanding the chronobiology of metabolic dysregulation 

We want to reveal the mechanisms behind the interaction between circadian rhythm, diet and exercise and metabolism and how these factors are influenced in type 2 diabetes. Disorders of the body’s internal clock increase the risk of metabolic diseases like type 2 diabetes. Synchronizing diet and exercise to the molecular circadian clock may maximize the health benefits on metabolism.

Intertissue communication in metabolic disease

We are exploring how altered inter-tissue communication plays a role in development of metabolic disease. To this end we are studying secreted peptides and hormones as well as metabolites and circulating miRNAs 

Multi-omic analysis in metabolic disease

We are harnessing large-scale omic analysis to identify molecular targets and disease mechanisms.

Role of non-coding RNA

We are working on elucidating the role of different non-coding RNAs in skeletal muscle insulin sensitivity. 

Inflammation, insulin resistance and immuno-metabolism

Our research team precisely aims to investigate the communications between skeletal muscle and the immune system under conditions of metabolic stress. Our primary objective is to understand how these interactions affect the development and progression of metabolic diseases, with an emphasis on type 2 diabetes.

Publications

Selected publications

Staff and contact

Group leaders

All members of the group

Visiting address

Karolinska Institutet, Fyfa and MMK, Solnavägen 9, Biomedicum 4c, Stockholm, Solna, 17177, Sverige