Relative Contribution of Brain Insulin Action for Postprandial Metabolism

Condition(s) studied

Investigational drug(s) / intervention(s)

Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray: Subjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. \[6,6-2H\]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Intranasal insulin will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose.

Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray: Subjects will undergo a 75 g OGTT (180 min) combined with a double tracer dilution. The double-tracer dilution technique will be used to quantify endogenous glucose production, glucose appearance and disappearance rate. \[6,6-2H\]glucose will be infused for a total of 300 minutes,while the infusion will start 120 minutes prior the OGTT and will last until the end of the OGTT. Placebo spray will be administered 15 minutes prior to the start of the OGTT. The drink consumed at time point 0 min contains 75 gram glucose, enriched with \[U-13C6\]-glucose. To mimic insulin spill-over from nasal spray into systemic circulation, an i.v. insulin bolus of 3 mU × kg-1. will be administered over ten minutes starting at time point -15 minutes on the placebo spray day. On the insulin spray day a comparable amount of saline will be infused.

Study summary

The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women.

Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.

Eligibility

Primary outcome measure(s)

• Endogenous glucose production — -120 minutes - 180 minutes during oral glucose tolerance test
  Effect of intranasal insulin versus placebo on endogenous glucose production assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
• Rate of glucose disappearance — -120 minutes - 180 minutes during oral glucose tolerance test
  Effect of intranasal insulin versus placebo on rate of glucose disappearance (Rd) assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.

Trial sites (1)

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