Hyperglycemia and the Extra-pancreatic Effect of Incretins

NCT01749163 | Completed

• 1 other identifier: PancClamp
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Incretin hormones (GLP-1 and GIP) released from the intestine in response to meal ingestion augment insulin secretion from the pancreas to help maintain glycemic control. Studies in vitro and in vivo have shown that these incretin hormones also have functional effects in other tissues independent of the insulin secretory response. Both GLP-1 and GIP stimulate insulin secretion in a glucose-dependent manner, however the glucose-dependency of their extra-pancreatic effects has not been examined in vivo. By using pancreatic clamp methodology during euglycemic and hyperglycemic conditions we will test the hypothesis that extra-pancreatic effects of GLP-1 and GIP are glucose-dependent.

Conditions

Extra-pancreatic Incretin Effect; Glucose Effectiveness

Outcome Measures

Primary Outcomes (2)

• Glucose metabolism

  Pancreatic clamp will be performed including infusion of somatostatin and replacement of basal insulin, glucagon, and growth hormone. During pancreatic clamps, euglycemia (5 mM) will be maintained via exogenous glucose infusion for the first 2-hours, followed by hyperglycemia (+5 mM) for the final 2-hours. An infusion of the stable isotope \[U13C\]glucose will be performed to assess glucose kinetics. Expired air will be collected for the analysis of \[U13C\]glucose into 13CO2.

  up to 4 hours

• Lipid metabolism

  An infusion of the stable isotope \[D5\]glycerol will be performed to assess glycerol kinetics.

  up to 4 hours

Secondary Outcomes (2)

• Endothelial function

  Baseline, 2 hours, and 4 hours

• Signaling

  Baseline, 2 hours, and 4 hours

Study Arms (3)

Control

EXPERIMENTAL

Saline will be coninfused during the pancreatic clamp

Biological: Saline

GIP

EXPERIMENTAL

GIP will be infused intravenously during the pancreatic clamp at 1.5 pmol/kg/min

Biological: GIP

GLP-1

EXPERIMENTAL

GLP-1 will be infused intravenously during the pancreatic clamp at 0.5 pmol/kg/min

Biological: GLP-1

Interventions

Saline BIOLOGICAL

Control

GIP BIOLOGICAL

GIP

GLP-1 BIOLOGICAL

GLP-1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• age 18-60 years
• BMI 18-30 kg/m2
• Male
• Normal glycemic control (fasting glucose \<5.6 mM)

You may not qualify if:

• Evidence of chronic disease
• Smoking
• Active weight loss (\>2 kg in previous 6 months)
• Treatment with drugs known to affect our outcome varaibles

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

Location

Related Publications (1)

• Solomon TPJ, Carter S, Haus JM, Karstoft K, von Holstein-Rathlou S, Nielsen MS, Gillum MP. Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans. PeerJ. 2022 Jan 19;10:e12755. doi: 10.7717/peerj.12755. eCollection 2022.

  PMID: 35111398 DERIVED

MeSH Terms

Interventions

Sodium Chloride; Glucagon-Like Peptide 1

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Thomas PJ Solomon, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: December 11, 2012
• First Posted: December 13, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: December 3, 2014

Record last verified: 2014-12

Locations

DK (1)