PRESERVED INCRETIN EFFECT IN TYPE-1 DIABETIC-PATIENTS WITH END-STAGE NEPHROPATHY TREATED BY COMBINED HETEROTOPIC PANCREAS AND KIDNEY-TRANSPLANTATION

Insulin secretion is stimulated better by oral than by intravenous glu cose (incretin effect). The contribution of the autonomic nervous syst em to the incretin effect after oral glucose in humans is unclear. We therefore examined nine type 1 diabetic (insulin-dependent) patients w ith end-stage nephropathy, studied after combined heterotopic pancreas and kidney transplantation, and 7 non-diabetic kidney recipients (mat ched for creatinine clearance and immunosuppressive medication). The r elease of gastric inhibitory polypeptide (GIP) and glucagon-like pepti de 1 (GLP-1) immunoreactivity and B cell secretory responses (IR insul in and C-peptide) to oral (50 g) and ''isoglycaemic'' intravenous gluc ose (identical glycaemic profile) were measured by radioimmunoassay. T he difference in B cell responses between the two tests represents the contribution of the enteroinsular axis to the response after oral glu cose (incretin effect). Insulin responses after the oral glucose chall enge were similar in the two patient groups despite systemic venous dr ainage of the pancreas graft in the pancreas-kidney-transplanted group . In both groups GIP and GLP-1 increased after oral but not after intr avenous glucose, and B cell secretory responses were significantly sma ller (by 55.2 +/- 7.7% and 46.5 +/- 12.5%, respectively) with ''isogly caemic'' intravenous glucose infusions. The lack of reduction in the i ncretin effect in pancreas-kidney-transplanted patients, whose functio ning pancreas is denervated, indicates a lesser role for the nervous s ystem and a more important contribution of circulating incretin hormon es in mediating the enteroinsular axis in man.