The study aims to investigate the effect of acute angiotensin receptor blockade on insulin action/insulin resistance and expressions of selected adipocytokines in subcutaneous adipose tissue in insulin-resistant subjects with type 2 diabetes and healthy controls.

Hypothesis: Changes in adipocytokine concentrations and/or expressions and different reactions to acute in vivo induced hyperinsulinemia and angiotensin receptor blockade will be found in patients with type 2 diabetes compared to healthy subjects. A significant relationships between insulin sensitivity and selected adipokines and intracellular fat content and high energy phosphates in soleus muscle will be documented in healthy individuals, while no significant relation will be found in patients with type 2 diabetes.

10-15 patients with type 2 diabetes and 10-15 healthy control subjects will be examined on an outpatient basis. The following examination will be carried out in each subject after 12 hrs fasting:

• Oral glucose tolerance test (75 g of glucose) (in healthy subjects to confirm the normal tolerance of glucose).
• Evaluation of insulin secretion after 1 mg of glucagon i.v.
• Hyperinsulinaemic (75 mIU/l) euglycemic clamp study lasting 4 hours combined with indirect calorimetry and biopsy of subcutaneous adipose tissue.
• Hyperinsulinemic (75 mIU/l) euglycemic clamp study lasting 4 hours combined with indirect calorimetry after losartan 100 mg given in the evening and in the morning before the study.
• Proton and phosphorus MR Spectroscopy.

Before (0 min), at 30 min and in the end of studies c) and d) the blood samples will be taken and biopsies of subcutaneous abdominal adipose tissue will be done.

• Insulin Resistance
• Type 2 Diabetes

• Procedure: Hyperinsulinaemia
  Hyperinsulinaemic (1 mU/kg/min) euglycaemic (5 mmol/l) clamp
• Drug: Losartan
  Acute administration of losartan 200mg total prior to clamp
• Procedure: Saline
  Infusion of Saline as a volume control intervention

• Experimental: Hyperinsulinaemia
  Hyperinsulinaemic (1 mU/kg/min) euglycaemic (5 mmol/l) clamp
  Intervention: Procedure: Hyperinsulinaemia
• Experimental: Losartan + hyperinsulinaemia
  Interventions:

  • Procedure: Hyperinsulinaemia
  • Drug: Losartan
• Placebo Comparator: Saline
  Infusion of Saline as a volume control intervention
  Intervention: Procedure: Saline

Inclusion Criteria:

1. Type 2 Diabetes treated with oral agents and/or diet
2. Healthy volunteers age- and sex-matched to type 2 diabetes, without any concomitant disease

Exclusion Criteria:

1. Type 2 Diabetes

   • treated with insulin
   • clinical evidence of atherosclerotic complications
   • advanced long-term diabetic complications (manifest nephropathy, proliferative retinopathy)
   • other internal disease
   • weight change >10% 3 months prior to study

2. Healthy volunteers

   • fulfilling the criteria of metabolic syndrome
   • weight change >10% 3 months prior to study