We want to investigate the mechanisms of extrapancreatic effects on gastrointestinal-mediated glucose disposal. In order to do so we will perform oral glucose tolerance tests and isoglycemic intravenous glucose infusions in total pancreatectomised patients and in healthy controls.

In the current project we wish to identify the possible contribution of extrapancreatic effects on gastrointestinal-mediated glucose disposal (GIGD). GIGD reflects the percentage of an individual's glucose disposal following oral glucose tolerance test (OGTT) which is caused by the oral route of glucose administration. In healthy subjects GIGD amounts to ~60%. GIGD describes not only the impact of the incretin effect (insulinotropic substances released upon intestinal stimulation) but includes all factors affecting glucose disposal differently during oral vs. iv administration of glucose (including neural reflexes, activation of afferent nerves in the intestinal mucosa, differences in glucagon secretion, hepatic glucose production and first-pass hepatic uptake of glucose, differences in portal and venous blood glucose concentrations and/or at the present unknown factors. It is likely that the incretin effect (pancreatic effect) constitutes a major contributor to GIGD, but so far it has been impossible to discriminate between pancreatic and extrapancreatic mechanisms underlying GIGD

Inclusion Criteria:

• Pancreatectomized patients

  • Caucasians above 18 years of age who have undergone total pancreatectomy
  • Normal haemoglobin
  • Informed consent Healthy Subjects
  • Normal fasting plasma glucose (FPG) and normal HbA1C (according to the World Health Organization (WHO) criteria)
  • Normal haemoglobin
  • Age above 18 years
  • Informed consent

Exclusion Criteria:

• Pancreatectomized patients

  • Inflammatory bowel disease
  • Operation within the last 3 months
  • Ongoing chemotherapy or chemotherapy within the last 3 months
  • Ostomy
  • Nephropathy (serum creatinine >150 µM and/or albuminuria)
  • Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3×normal values)
  • Pregnancy and/or breastfeeding
  • Age above 80 years
  • Any condition that the investigator feels would interfere with trial participation Healthy Subjects
  • Diabetes mellitus (DM)
  • Prediabetes (impaired glucose tolerance and/or impaired FPG)
  • First degree relatives with DM
  • Inflammatory bowel disease
  • Intestinal resection and/or ostomy
  • Nephropathy (serum creatinine >150 µM and/or albuminuria
  • Liver disease (ALAT and/or serum ASAT >2×normal values)
  • Pregnancy and/or breastfeeding
  • Age above 80 years
  • Any condition that the investigator feels would interfere with trial participation

Patients operated at/or cared for at the endocrinology out-patient-clinic, Rigshospitalet, University of Copenhagen, Copenhagen Denmark