In this study the investigators would like to elaborate on the mechanisms that lead to a higher insulin sensitivity after exercise training and a lower insulin sensitivity after bedrest.

The investigators speculate that the concomitant chances in blood volume during training and bedrest might explain the changed insulin sensitivity because with a changing blood volume also the dilution space of the glucose will change.

Furthermore, the investigators would like to work on the influence of a changed capacity of skeletal muscle for glucose uptake and glycogen storage on the glucose sensitivity.

Therefore, A) a bed rest study with healthy untrained subjects and B) a training study with obese pre-diabetic patients will be conducted.

While there is little doubt that physical inactivity leads to reduced insulin sensitivity and in contrast hereto that physical activity improves insulin sensitivity the underlying mechanisms are still to a large extend unknown. With this study the investigators wish to test two independent hypotheses that may explain the observed changes:

The first hypothesis is that part of the explanation for the known increase in circulating levels of glucose in response to an oral glucose tolerance test (indicating reduced insulin sensitivity) following bed rest is due to a concomitantly reduced blood volume and thereby dilution space.

In addition the investigators also speculate that the reduced glucose response to an oral glucose tolerance test (indicating improved insulin sensitivity) after a training period is related to the exercise induced increase in blood volume, and hence an increased dilution space.

Based on this, the hypothesis to be tested with these two experimental approaches (bed rest and aerobic exercise training), is that at least part of the changes observed in the glucose tolerance following bed rest and aerobic exercise training are related to concomitantly occurring changes in blood volume.

The second hypothesis to be tested is that another important contributor to the changes in circulating glucose levels following an oral glucose tolerance test after bed rest and physical training are related to diminished or improved capacity for skeletal muscle glucose uptake and glycogen storage, respectively. The rationale here fore are that exercise training increases skeletal muscle glycogen content and storage capacity in healthy and type 2 diabetic patients, respectively, and that bed rest does the opposite.

To test this hypothesis two different intervention studies will be conducted. Study 1 is a bed rest study with healthy untrained subjects and study 2 is a training study with obese "pre-diabetic patients".

Bedrest:

Inclusion Criteria:

• Informed consent as documented by signature
• Age: 18-35
• healthy (no chronic diseases)
• BMI: 19-25
• maximal oxygen uptake: 35-50 ml O2/min/kg

Exclusion Criteria:

• chronic diseases
• any health problems that do not allow the subjects to participate in the measurements (i.e. heart defect)
• History of familiar history (1st grade relatives) of venous thrombic-embolism or renal insufficiency
• Blood donation in the last month
• Any medication with known influence on blood volume, glucose metabolism and body weight
• Stay above 2500 m for more than 1 day
• Known allergies against Fragmin or Heparin

Training:

Inclusion criteria:

• Informed consent as documented by signature
• Age: 35-50
• BMI: 30-40
• Fat%: 30-40 %
• maximal oxygen uptake: 20-35 ml O2/min/kg
• HbA1c: 5.5 - 7.0 %

Exclusion criteria:

• Chronic diseases
• Any health problems that do not allow the subjects to participate in the measurements (i.e. heart defect)
• Blood donation in the last month
• Any medication with known influence on blood volume, glucose metabolism and body weight
• Stay above 2500 m for more than 1 day