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


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/m2) ate a mixed meal, and 30 microg 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 micromol.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.
Woerle
H-J
HJ
Dept. of Internal Medicine II, Clinical Research Unit, Univ. of Munich, LMU, Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. Hans-Juergen.Woerle@med.uni-muenchen.de
Albrecht
M
M
Linke
R
R
Zschau
S
S
Neumann
C
C
Nicolaus
M
M
Gerich
J
J
Göke
B
B
Schirra
J
J
D000328:Adult; D000682:Amyloid / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000097:blood; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D008297:Male; D010919:Placebos; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology*; D012044:Regression Analysis; D013152:Splanchnic Circulation / Q000502:physiology; D013997:Time Factors
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010919:Placebos; D005934:Glucagon; C105254:pramlintide