The Glucose-Independent Effects of Exogenous Glucagon on Insulin Secretion and Cognitive Function in Healthy Subjects

Investigating the Effect of Glucagon on Cognitive Function and Cerebral Glucose Metabolism in Humans: A Pilot Study

In this study the investigators will investigate the glucose-independent effects of exogenous glucagon on insulin secretion and cognitive function in healthy subjects.

Subjects will participate in two study days. The first study day is with a 240-minute infusion of glucagon and the second study day is with an infusion of glucose (clamped to match the glucose levels measured during the glucagon infusion). During the study day, blood samples will be drawn frequently and cognitive testing will be performed.

The investigators will investigate glucagon's glucose-independent effects on insulin secretion and cognitive function by comparing plasma measures of C-peptide and cognitive test scores between the glucagon study day and the glucose clamp study day.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism; Insulin Secretion
• Intervention / Treatment: Other: Glucagon Infusion; Other: Glucose clamp

Detailed Description

Five-ten subjects with normal health will be included, and each subject will participate in two study days.

Participants will arrive after an overnight fast and will be placed in a hospital bed in a semi-recumbent position. In each antecubital vein an intravenous catheter will be placed; one for administration of glucagon or glucose and one for blood sampling. The first study day will be the glucagon study day. The blood measurements of glucose from the glucagon study day will be used for clamping the glucose levels during the glucose clamp study day.

Baseline blood samples will be drawn. At time 0 minutes the infusion of glucagon or glucose will be initiated. Glucagon will be infused at a rate of 10ng/kg/min. Blood glucose will be measured every five minutes for the first approximately 2.5 hours, and thereafter every 10-15 minutes. During the glucose-clamp study day the infusion rate of glucose will be adjusted continuously to match the glucose levels measured on the glucagon study day.

Blood samples for the analysis of plasma glucagon, insulin, C-peptide etc. will be drawn every five minutes for the first 60 minutes, and thereafter every 15-30 minutes.

After approximately three hours cognitive testing will be performed. After four hours, the infusion of either glucagon or glucose will be terminated. The final blood samples will be drawn 15 and 30 minutes after termination of the infusion.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Capable of understanding the participant information and signing the consent form
• Between 25 and 70 years of age at the time of screening
• Body mass index (BMI) ≤ 25 kg/m2 at the time of screening
• A minimum of 7 years of schooling

Exclusion Criteria:

• Enrolment in other research projects that might interfere with the study
• Diabetes diagnosis (type 1 and 2)
• Pregnancy or breastfeeding
• 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 function defined as either alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) ≥ 2 times normal values
• Kidney disease defined as serum creatinine levels ≥ 126 μmol/L for male and ≥ 111 μmol/L for female

• 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
• Inability to perform neuropsychological tests judged by the investigator (e.g. visual or auditory impairment or language barriers)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glucagon infusion followed by glucose-clamp; The first study day is a 240 minutes infusion of glucagon (10ng/kg/min). The second study day is a 240 minutes infusion of glucose (20% w/v). The infusion rate of glucose will be adjusted continuously to match the levels of glucose measured on the glucagon study day.	Other: Glucagon Infusion; A 240 minutes infusion of glucagon (10 ng/kg/min); Other: Glucose clamp; A 240 minutes infusion of 20 % w/v glucose. The infusion rate of glucose will be adjusted continuously to match the levels of glucose measured on the glucagon study day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide (0-90 minutes)	Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-90 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-peptide deconvolution (0-240 minutes)	Difference in deconvolution of plasma concentrations of C-peptide between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
Time to glucagon peak	Time to glucagon peak on the glucagon study day	During intervention (0-240 minutes)
Time to glucagon steady state	Time to glucagon steady state on the glucagon study day	During intervention (0-240 minutes)
Glucagon concentration at steady state	Plasma glucagon steady state concentration on the glucagon infusion study day	During intervention (0-240 minutes)
Glucose peak	Difference in plasma glucose peak concentration between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
Time to glucose peak	Difference in time to plasma glucose peak concentration between the glucagon infusion study day and the glucose clamp study day	During intervention (0-time to plasma glucose peak concentration (assessed up to two hours)
Glucose infused	Glucose (g) infused on the glucose clamp study day	During intervention (0-240 minutes)
Cognitive function	Difference in cognitive function assessed as a composite score from the cognitive testing (SCIP testing) between the glucagon infusion study day and the glucose clamp study day	During intervention (180-240 minutes)
C-peptide to glucose ratio (0-90 minutes)	Difference in plasma concentration of C-peptide assessed as area under the curve divided by plasma concentration of glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-90 minutes)
C-peptide to glucose ratio (0-240 minutes)	Difference in plasma concentration of C-peptide assessed as area under the curve divided by plasma concentration of glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
C-peptide (0-240 minutes)	Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
C-peptide (0 minutes-glucose peak)	Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-time to plasma glucose peak concentration (assessed up to two hours))
Insulin (0-90 minutes)	Difference in plasma concentrations of insulin assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-90 minutes)
Insulin (0-240 minutes)	Difference in plasma concentrations of insulin assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
Glucose (0-90 minutes)	Difference in plasma glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-90 minutes)
Glucose (0-240 minutes)	Difference in plasma glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
cAMP (0-90 minutes)	Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-90 minutes)
cAMP (0-240 minutes)	Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)
cAMP (240-300 minutes)	Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (240-300 minutes)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Word recall cognitive test	Difference in the word recall cognitive test between the glucagon infusion study day and the glucose clamp study day	During intervention (180-240 minutes)
Three-letter recall cognitive test	Difference in the three-letter recall cognitive test between the glucagon infusion study day and the glucose clamp study day	During intervention (180-240 minutes)
Verbal fluency cognitive test	Difference in the verbal fluency cognitive test between the glucagon infusion study day and the glucose clamp study day	During intervention (180-240 minutes)
Delayed word recall cognitive test	Difference in the delayed word recall cognitive test between the glucagon infusion study day and the glucose clamp study day	During intervention (180-240 minutes)
Visuomotor cognitive test	Difference in the visuomotor cognitive test between the glucagon infusion study day and the glucose clamp study day	During intervention (180-240 minutes)
Triglycerides (0-240 minutes)	Difference in plasma concentration of triglycerides assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day	During intervention (0-240 minutes)

Collaborators and Investigators

• Sponsor: Nicolai Jacob Wewer Albrechtsen
• Investigators: Principal Investigator: Nicolai J Wewer Albrecthsen, MD PhD, Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Actual): July 21, 2025
• Study Completion (Actual): July 21, 2025

Study Registration Dates

• First Submitted: November 6, 2024
• First Submitted That Met QC Criteria: November 11, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cognition; Glucagon; Insulin secretion; C-peptide; Glucose Metabolism; Glucose clamp
• Additional Relevant MeSH Terms: Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Blood Chemical Analysis; Clinical Chemistry Tests; Glucose Clamp Technique
• Other Study ID Numbers: GluCoMet_pilotB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No