Intact Liver Innervation and Glucose and Glucagon-like Peptide-1 (GLP-1) Induced Insulin Secretion

Condition(s) targeted: Liver Transplantation

Intervention: dipeptidyl peptidase 4 (DPP4) inhibitor (Drug); oral glucose (Other); intravenous glucose (Other)

Phase: N/A

Status: Recruiting

Sponsored by: University Hospital, Gentofte, Copenhagen

Overall contact:
Astrid Plamboeck, M.D., Phone: +45 26208174, Email: astridp@sund.ku.dk

The aim of the study is to investigate the significance of intact nerve supply to the liver for the glucagon-like peptide-1 (GLP-1) induced insulin secretion. The hypothesis is that the effects of GLP-1 is transmitted through the GLP-1 receptor and that these effects involve sensory afferent neurons, probably primarily parasympathetic.

Official title: The Significance of Intact Liver Innervation for the Glucose and GLP-1 Induced Insulin Secretion

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome: insulin secretion

Secondary outcome:

plasma glucose

plasma GLP-1

plasma GIP

plasma glucagon

plasma GLP-2

plasma PYY

Detailed description: GLP-1 is a potent enterogastron and incretin hormone. It is rapidly inactivated by dipeptidyl peptidase IV so only 10-15% enters the systemic circulation. This has led to the hypothesis that GLP-1 interact locally with afferent sensory nerve fibers. The aim of this study is to investigate the significance of intact liver innervation for the GLP-1 induced insulin secretion in liver transplanted patients; kidney transplanted control patients matched for immunosuppressive treatment, age, gender and body weight; and ten control persons matched for age, gender and body weight. The insulin secretion will be evaluated from blood samples that will be analyzed for insulin and c-peptide.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- normal fasting plasma glucose

- normal hemoglobin

- informed consent

Exclusion Criteria:

- type 1 diabetes mellitus or type 2 diabetes mellitus

- body mass index > 30

- inflammatory bowel disease

- intestinal surgery

- serum creatinine > 250 µM and/or albuminuria

- ALAT > 2 x normal value

- Severe cardiac insufficiency

- in treatment with medicine which cannot be paused for 12 hours

Astrid Plamboeck, M.D., Phone: +45 26208174, Email: astridp@sund.ku.dk

Department of Internal Medicine F' laboratory, Hellerup, Copenhagen 2900, Denmark; Recruiting
Astrid Plamboeck, M.D., Phone: +45 26208174, Email: astridp@sund.ku.dk
Tina Vilsbøll, M.D., Phone: +45 39772461, Email: tivi@geh.regionh.dk
Astrid Plamboeck, M.D., Principal Investigator

Starting date: July 2009
Last updated: January 5, 2012