The Effect of Glucagon on Cerebral Glucose Metabolism in Healthy Humans

This is a pilot study in which the investigators will investigate the effect of exogenous glucagon on cerebral glucose metabolism in healthy humans.

Participants will participate in either part C or part D of the study, and each participant will participate in three study days. During a study day the participant will receive an intravenous infusion of either glucagon, glucose (in an adjustable rate to match to glucose concentrations achieved with the glucagon infusion) or saline. During each study day an 18F-flouro-deoxy-glucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) scan will be performed to quantify cerebral glucose metabolism during the first part (acute effect) of the glucagon/glucose/saline infusion (part C) or the last part (later effect) of the glucagon/glucose/saline infusion (part D).

Participants in this study will participate in four visits; one screening visit and three study days.

Participants will be instructed to avoid strenuous exercise and alcohol intake two days prior to each experimental visit. Participants will arrive at the Department of Clinical Physiology and Nuclear Medicine after an overnight (\>10 hours) fast (including coffee and medicine).

On all three study days, two peripheral venous catheters will be placed in the antecubital vein of each arm (one for the collection of blood samples and one for infusions). After two initial blood samples the infusion of either saline, glucagon or glucose will be started. The infusion rate of glucagon will be 10 ng/kg/min. The infusion rate of glucose will be adjustable, and adjusted to match the blood glucose levels achieved on the glucagon study day.

During the infusion of saline, glucagon or glucose a 18F-FDG PET/CT scan will be performed. The 18F-FDG PET/CT scan will be performed either in the beginning of the infusions (approximately 15-55 min after the start of infusion) (for participants in part C) or in the end of the infusions (approximately 150-190 min after the start of infusion) (for participants in part D).

Eligibility Criteria:
Inclusion Criteria:

* Age 55 to 70 years
* BMI under or equal to 30 kg/m2
* Capable of understanding the participant information and signing the consent form

Exclusion Criteria:

* Enrolment in other research projects that might interfere with the study
* Diabetes diagnosis (type 1 and 2)
* Use of medications which, in the opinion of the investigator, may jeopardise participant's safety or compliance with the protocol
* Diagnosis of psychiatric disorders, dementias, or any other neurological disorders that in the opinion of the investigator precludes compliance with the study protocol, evaluation of the results or represents an unacceptable risk for the participants safety
* Severe claustrophobia
* Impaired liver og kidney function
* Cardiac problems including any of the following:

  1. Classified as being in New York Heart Association (NYHA) class III or IV
  2. Angina pectoris (chest pain) within the last 6 months
  3. Acute myocardial infarction (heart attack) within last 2 years
* Inadequately treated blood pressure at screening defined as repeated resting blood pressure outside the range 90-150 mmHg for systolic and 50-100 mmHg for diastolic.
* Active or recent malignant disease
* Current or history of severe alcohol use or drug/chemical abuse as per investigator's judgement
* Any chronic disorders or severe diseases which, in the opinion of the investigator, might jeopardise participant's safety or compliance with the protocol