SRP Diabetes is centred on a few important research areas reflecting the situation for the world-wide prevalence of diabetes, with approximately ~90 % of patients diagnosed as type 2 diabetic and ~10 % as type 1 diabetic. Thirty-five different principal investigators are affiliated to the programme.
Islet Cell Biology
Researchers within the programme have made significant discoveries elucidating how pancreatic islets and beta cells develop, and have contributed seminal findings delineating the intracellular components regulating the release of insulin. Unique methodologies based on advanced microscopy have been developed to enable the study of these processes in situ. Currently, the study of the complex molecular mechanisms involved in the regulation of human islet cell function and survival under physiological conditions in vivo is underway to probe the role of the islet cell in diabetes pathogenesis. Ongoing research also focuses on improving methodology for transplantation of islets to patients. Overall, the programme aims to identify novel targets for the treatment of Type 2 diabetes and predictive markers for beta cell function and survival in islet transplantation in Type 1 diabetes.
Peripheral Mechanisms Controlling Insulin Action and Energy Homeostasis
Defining the physiological role of novel and previously identified candidate genes/proteins linked to Type 2 diabetes is a central research focus. Model organisms are utilized to assess the functional role of these targets in Type 2 diabetes pathogenesis. Detailed metabolic studies are performed to determine genotype/phenotype interactions and to identify diabetes risk-factors. Novel findings stemmed from this focus are valuable for developing therapies and improving public health interventions through population screening programs.
b) Inter and Intracellular and Organ Communication
Intercellular and intracellular communication within and between organs is fundamental for the control of glucose and lipid homeostasis. This delicate balance is altered in the context of Type 1 and Type 2 diabetes. Research within the programme is designed to identify and integrate inter and intracellular signalling pathways controlling glucose and lipid homeostasis, harnessing the expertise of several different participating research groups including beta cell, muscle and fat physiology. The aim of this focus is to validate diabetes prevention and treatment targets.
c) Energy Intake and Expenditure
Obesity, inadequate nutrition, and lack of physical activity are major risk factors for Type 2 diabetes. The increasing prevalence of obesity in Sweden is becoming an emerging challenge for the Swedish public health care system. To this point, researchers within the programme have identified and characterised molecular and physiological mechanisms by which diet composition (percentage of carbohydrates, fat and protein) affects appetite, hormonal response, and inflammation levels in healthy people, pre-diabetic people and people with Type 1 or Type 2 diabetes. Efforts are also focused on characterising the molecular mechanisms behind how weight loss and exercise can improve insulin sensitivity in both healthy and diabetic individuals. Unravelling the molecular mechanisms regulating these responses may provide novel insights into the treatment and prevention of both Type 1 and Type 2 diabetes, as well as diabetes-related complications.
Identifying Risk Factors for Diabetes and Diabetes-Related Complications in order to Improve Prevention
Large-scale epidemiological research has been conducted to identify risk factors that predispose the population to the development of pre-diabetes (impaired tolerance to sugar) and eventually overt Type 2 diabetes. In individuals with pre-diabetes, as well as newly onset Type 2 diabetes, lifestyle modification, including increased exercise and/or calorie restriction, is often able to reverse disease progression. The programme aims to delineate novel risk factors, including genetic susceptibility, to understand the impact of specific lifestyle modifications, and to identify the impact of stress, sleep deprivation, smoking and intake of alcohol.
Macro- and Micro-Vascular Complications
Diabetes-related complications due to specific organ and/or tissue dysfunction are the greatest cause of morbidity and mortality in Type 1 and Type 2 diabetes. Complications include increased risk of coronary heart disease, stroke and peripheral vascular disease (macro-vascular disease), as well as nephropathy, retinopathy and neuropathy (micro-vascular disease), and impaired wound healing which increases the risk of amputation. Researchers in the programme aim to identify the faulty molecular mechanisms and genes underlying the development of complications and detection of high-risk individuals. The primary goal is to establish gene expression signatures and to validate clinical surrogate biomarkers that mark the progression of diabetes-related complications.