Effects of Intranasal Insulin Administration on Tissue Specific Insulin Sensitivity

Summary

Recent research has suggested that intranasally administered insulin can reach the brain quickly without passing through circulation and evoke increased insulin sensitivity and tissue glucose consumption during insulin stimulation (low-dose hyperinsulinemic, euglycemic clamp). It is still not known what mechanism causes these changes or what tissues are involved in this.

In this study, the changes in tissue-specific insulin sensitivity and glucose uptake will be investigated by using glucose-analogue radiotracer (\[18F\]-fluorodeoxyglucose) with positron emission tomography (PET) imaging during insulin stimulation. Ten healthy males are studied, each receiving nasal sprays containing insulin or placebo in a randomized order on two separate days. After spray administration, glucose uptake in skeletal muscle, liver, subcutaneous and visceral adipose tissue, myocardium, intestines, brown adipose tissue and brain assessed by PET imaging and glucose uptake in these tissues is analyzed. Endogenous glucose production is calculated facilitating the measurements glucose and radiotracer uptake in tissues and tracer loss into urine.

As skeletal muscle consumes most of the glucose available, it is likely that administration of insulin sprays will result in an increased uptake in this tissue. Some increase in glucose uptake might also be seen in other tissue types after insulin spray versus placebo spray administration.

Conditions

• Insulin Resistance

Interventions

DRUG

Actrapid

Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays or 160 IU of fast-acting human insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd, Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray.

DRUG

Placebo

Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain Insulin Diluting Medium for Novorapid and Levemir (Novo Nordisk A/S, Bagsvaerd, Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd, Denmark) over 15 minutes.

RADIATION

[18F]-FDG PET-CT

All subjects will undergo two positron emission tomography (PET) studies. On both visits they are injected with 185 MBq \[18F\]-fluorodeoxyglucose and scanned with a combined PET and computed tomography scanner.

DRUG

Hyperinsulinemic euglycemic clamp

All subjects will undergo two hyperinsulinemic euglycemic clamp studies. The insulin infusion will be administered intravenously at a steady rate of 0.25 mU/kg/min for approximately 170 minutes. Glucose will be administered intravenously as a 200 mg/ml fluid to at varying rate to maintain euglycemia.

Sponsors & Collaborators

• University Hospital Tuebingen

  collaborator OTHER

• Turku University Hospital

  lead OTHER_GOV

Principal Investigators

• Pirjo Nuutila, MD,PhD · Turku University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

20 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-04-30

Primary Completion

2016-12-31

Completion

2016-12-31

Countries

• Finland

Study Locations