A Study of Intracellular Signaling in Muscle and Fat Cells During Ketosis

The Role of ATGL and G0/G1 Switch Gene Complex in Lipopolysaccaride (LPS) Induced Ketosis - a Controlled, Randomised, Clinical Experimental Study

Hypothesis

1. To define whether stimulation of ATGL and suppression of G0/G1 switch gene occur in the initial phases of diabetic ketoacidosis and thus can be identified as the primary mechanisms behind this life threatening condition.
2. Make a human model for studying ketoacidosis.

The investigators plan to reduce in their regular insulin over night. In the morning we administer endotoxin, which together with a relative lack of insulin will initiate ketogenesis - a state of ketoacidosis. On another occasion strict glycemic control is imposed by means of intravenous insulin. The testing is done two separate days with at least 3 weeks in between and patients are admitted to hospital the evening before the day of testing. The investigators use isotopic tracers to determine metabolic fluxes and analyse fat (ATGL, G0/G1 switch gene) and muscle biopsies.

Inclusion Criteria:

• Diabetes type 1
• 19 < BMI < 26
• minimal or negative C-peptide
• written consent

Exclusion Criteria:

• Severe comorbidity
• regular medication apart from insulin