title: Preserved incretin effect in type 1 diabetic patients with end-stage nephropathy treated by combined heterotopic pancreas and kidney transplantation.
abstract: Insulin secretion is stimulated better by oral than by intravenous glucose (incretin effect). The contribution of the autonomic nervous system to the incretin effect after oral glucose in humans is unclear. We therefore examined nine type 1 diabetic (insulin-dependent) patients with end-stage nephropathy, studied after combined heterotopic pancreas and kidney transplantation, and 7 non-diabetic kidney recipients (matched for creatinine clearance and immunosuppressive medication). The release of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) immunoreactivity and B cell secretory responses (IR insulin and C-peptide) to oral (50 g) and "isoglycaemic" intravenous glucose (identical glycaemic profile) were measured by radioimmunoassay. The difference in B cell responses between the two tests represents the contribution of the enteroinsular axis to the response after oral glucose (incretin effect). Insulin responses after the oral glucose challenge were similar in the two patient groups despite systemic venous drainage of the pancreas graft in the pancreas-kidney-transplanted group. In both groups GIP and GLP-1 increased after oral but not after intravenous glucose, and B cell secretory responses were significantly smaller (by 55.2 +/- 7.7% and 46.5 +/- 12.5%, respectively) with "isoglycaemic" intravenous glucose infusions. The lack of reduction in the incretin effect in pancreas-kidney-transplanted patients, whose functioning pancreas is denervated, indicates a lesser role for the nervous system and a more important contribution of circulating incretin hormones in mediating the enteroinsular axis in man.
authors.affiliation: Department of Medicine, Georg August University, Göttingen, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Nauck
authors.forename: M
authors.initials: M
authors.lastname: Büsing
authors.forename: C
authors.initials: C
authors.lastname: Orskov
authors.forename: E G
authors.initials: EG
authors.lastname: Siegel
authors.forename: J
authors.initials: J
authors.lastname: Talartschik
authors.forename: A
authors.initials: A
authors.lastname: Baartz
authors.forename: T
authors.initials: T
authors.lastname: Baartz
authors.forename: U T
authors.initials: UT
authors.lastname: Hopt
authors.forename: H D
authors.initials: HD
authors.lastname: Becker
authors.forename: W
authors.initials: W
authors.lastname: Creutzfeldt
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology* / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism; D011863:Radioimmunoassay; D012016:Reference Values; D016042:Transplantation, Heterotopic
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose