Importance of changes in gastric emptying for postprandial plasma glucose fluxes in healthy humans

• Published in: American journal of physiology: endocrinology and metabolism Vol. 294; no. 1; pp. E103 - E109
• Main Authors: Woerle, H.-J, Albrecht, M, Linke, R, Zschau, S, Neumann, C, Nicolaus, M, Gerich, J, Goke, B, Schirra, J
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2008
• Subjects: Adult; Amyloid - administration & dosage; Blood Glucose - metabolism; Female; Gastric Emptying - drug effects; Gastric Emptying - physiology; Glucagon - blood; Glucose; Homeostasis - drug effects; Homeostasis - physiology; Humans; Hyperglycemia; Hypoglycemic Agents - administration & dosage; Insulin; Insulin - blood; Islet Amyloid Polypeptide; Male; Meals; Placebos; Postprandial Period - drug effects; Postprandial Period - physiology; Regression Analysis; Splanchnic Circulation - physiology; Time Factors
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00514.2007

1 Department of Internal Medicine II, Clinical Research Unit, and 2 Department of Nuclear Medicine, Grosshadern, Ludwig-Maximilians-University, Munich; 3 Outpatient Diabetes Center, Leopoldstrasse, Munich, Germany; and 4 Department of Medicine, University of Rochester School of Medicine, Rochester, New York Submitted 8 August 2007 ; accepted in final form 19 October 2007 Objective: Regulation of postprandial (pp) plasma glucose excursions is complex. Insulin and glucagon are thought to play the predominant role. Nevertheless, only 50% of the variation in pp plasma glucose excursions is explained by variations by the latter. Theoretically, gastric emptying (GE) should be another important factor. However, its impact on pp glucose homeostasis is unknown. Research Design and Methods: We examined the consequences of pramlintide-induced delay in GE on pp glycemia and glucose fluxes, determined isotopically. GE was recorded by scintigraphy. Fourteen healthy subjects (8 men, 6 women; age 40 ± 3 yr, body mass index 27.8 ± 1.1 kg/m 2 ) ate a mixed meal, and 30 µg of pramlintide (PRAM) or placebo (PBO) were injected subcutaneously. Results: At 60 min, greater proportions of the initial gastric contents remained in the stomach (PBO vs. PRAM). Thereafter, GE slopes paralleled until 240 min. Fifty percent retention times were lower when PBO was given ( P < 0.001). GE was greater from 240 min to the end of the PRAM experiments, so that only slightly greater proportions of the meal remained in the stomach at 330 min. Reductions of GE lowered pp glucose (7.5 ± 0.3 vs. 6.0 ± 0.2 mmol/l, P < 0.001), even though plasma insulin was lower with PRAM (164 ± 13 vs. 138 ± 13 pmol/ml, both P < 0.01). Reduction in total glucose appearance ( P < 0.001) was due to reduced meal-derived glucose appearance (10.2 ± 0.5 vs. 7.0 ± 0.4 µmol·kg –1 ·min –1 , P < 0.001). Endogenous glucose appearance was greater with PRAM ( P < 0.001). Splanchnic glucose uptake was greater with PRAM (26.5 ± 1.6 vs. 32.5 ± 2.1%, P = 0.014). Conclusions: These data support the concept that GE is an important physiological regulator of pp glucose homeostasis in humans. Address for reprint requests and other correspondence: H.-J. Woerle, Dept. of Internal Medicine II, Clinical Research Unit (CRU), Univ. of Munich, LMU, Grosshadern, Marchioninistr. 15, 81377 Munich, Germany (e-mail: Hans-Juergen.Woerle{at}med.uni-muenchen.de )