Abstract
The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min−1 over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut–incretin axis.
Highlights
Roux-en-Y gastric bypass leads to remarkable improvements in glycaemic control in type 2 diabetes, associated with an enhanced incretin effect (the phenomenon of an amplified insulin response to enteral vs intravenous (i.v.) glucose, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)).[1,2]
We hypothesised that bypassing the duodenum would elicit a greater response of the gut–incretin axis to small intestinal glucose infusion, and compared plasma GLP-1, GIP, insulin and glucagon, and blood glucose responses to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans
We showed that i.j. glucose elicited greater incretin and insulin release than i.d. glucose in healthy males, supporting the concept that directing nutrients more distally in the small intestine could ameliorate type 2 diabetes
Summary
Roux-en-Y gastric bypass leads to remarkable improvements in glycaemic control in type 2 diabetes, associated with an enhanced incretin effect (the phenomenon of an amplified insulin response to enteral vs intravenous (i.v.) glucose, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)).[1,2] This may relate to diversion of nutrients more distally in the small intestine, as similar benefits are observed with the endoluminal sleeve device.[3]. Plasma total GLP-1 was measured by radioimmunoassay (GLP1T-36HK; Linco Research, St Charles, MO, USA) with a sensitivity of 3 pmol l − 1, and intra- and inter-assay coefficients of variation (CVs) of 6.8% and 8.5%, respectively. Plasma total GIP was measured by radioimmunoassay modified from a previously published method,[5] with a sensitivity of 2 pmol l − 1, and intra- and inter-assay CVs of 5.1%. Plasma insulin was measured by enzymelinked immunosorbent assay (10-1113; Mercodia, Uppsala, Sweden) with a sensitivity of 1 mU l − 1 and intra- and inter-assay CVs of 2.7% and 7.8%, respectively. Plasma glucagon was measured by radioimmunoassay (GL-32 K; Millipore, Billerica, MA, USA) with a sensitivity of 20 pg ml − 1, and intra- and inter-assay. Data are represented as mean ± s.e.; Po 0.05 (two sided) was considered statistically significant
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