scholarly journals Mechanisms of the antidiabetic action of subcutaneous glucagon-like peptide-1(7-36)amide in non-insulin dependent diabetes mellitus

1998 ◽  
Vol 156 (1) ◽  
pp. 177-186 ◽  
Author(s):  
J Schirra ◽  
P Leicht ◽  
P Hildebrand ◽  
C Beglinger ◽  
R Arnold ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gastric Emptying ◽  
Insulin Dependent Diabetes Mellitus ◽  
Postprandial Glucose ◽  
Dependent Diabetes Mellitus ◽  
Solid Meal ◽  
Insulin Dependent ◽  
Lag Period ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Twelve patients with non-insulin dependent diabetes mellitus (NIDDM) under secondary failure to sulfonylureas were studied to evaluate the effects of subcutaneous glucagon-like peptide-1(7-36)amide (GLP-1) on (a) the gastric emptying pattern of a solid meal (250 kcal) and (b) the glycemic and endocrine responses to this solid meal and an oral glucose tolerance test (OGTT, 300 kcal). 0.5 nmol/kg of GLP-1 or placebo were subcutaneously injected 20 min after meal ingestion. GLP-1 modified the pattern of gastric emptying by prolonging the time to reach maximal emptying velocity (lag period) which was followed by an acceleration in the post-lag period. The maximal emptying velocity and the emptying half-time remained unaltered. With both meals, GLP-1 diminished the postprandial glucose peak, and reduced the glycemic response during the first two postprandial hours by 54.5% (solid meal) and 32.7% (OGTT) (P < 0.05). GLP-1 markedly stimulated insulin secretion with an effect lasting for 105 min (solid meal) or 150 min (OGTT). The postprandial increase of plasma glucagon was abolished by GLP-1. GLP-1 diminished the postprandial release of pancreatic polypeptide. The initial and transient delay of gastric emptying, the enhancement of postprandial insulin release, and the inhibition of postprandial glucagon release were independent determinants (P < 0.002) of the postprandial glucose response after subcutaneous GLP-1. An inhibition of efferent vagal activity may contribute to the inhibitory effect of GLP-1 on gastric emptying.

Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)—evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins

1996 ◽  
Vol 135 (4) ◽  
pp. 425-432 ◽  
Author(s):  
Allan A Vaag ◽  
Jens J Holst ◽  
Aage Vølund ◽  
Henning Beck-Nielsen
Keyword(s):  
Family History ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Oral Glucose ◽  
Family History Of Diabetes ◽  
Glucose Ingestion ◽  
Insulin Dependent ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Vaag AA, Holst JJ, Volund A, Beck-Nielsen H. Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)—evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins. Eur J Endocrinol 1996;135:425–32. ISSN 0804–4643 The incremental glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses (areas under curves; AUCs) were determined during a standard 180-min 75-g oral glucose tolerance test in a group of 12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) and 13 matched controls without family history of diabetes using highly sensitive and specific radioimmunoassay hormone assays. Data were analysed using multifactor analysis of variance (ANOVA) to identify and correct for possible covariates and to correct for multiple comparisons. Fasting plasma GLP-1 and GIP concentrations were similar in all groups. The twins with frank NIDDM had a decreased incremental GLP-1 response during oral glucose ingestion compared with controls without family history of diabetes (AUC±sem; 0.55 ± 0.14 vs 1.17 ± 0.25 (mmol/l) × min, p < 0.05). The incremental GLP-1 secretion in the non-diabetic twins was not significantly different from neither their NIDDM co-twins nor the controls without family history of diabetes. The incremental GIP responses were similar in all study groups. Gender was identified as the major independent covariate for incremental glucose, insulin, GIP and GLP-1 responses, with higher values of all parameters in females. Waist-to-hip ratio and body mass index (BMI) were identified as independent but oppositely directed covariates for the incremental GLP-1 responses (waist-to-hip ratio: r = 0.43, p < 0.02; BMI: r= −0.34, p = 0.06). Incremental GLP-1 responses correlated with incremental insulin responses in the combined study population (N = 37; R = 0.42, p = 0.01). In conclusion, a decreased intestinal GLP-1 secretion may contribute to the abnormal insulin secretion during oral glucose ingestion in NIDDM twins. However, decreased secretion of gut incretin hormones (GLP-1 or GIP) does not explain all of the defects of pancreatic insulin secretion in NIDDM patients/twins or in non-diabetic individuals (identical twins) with a genetic predisposition to NIDDM. Allan Vaag, Odense University Hospital, Department of Endocrinology and Internal Medicine M, Sdr. Boulevard, Odense, DK-5000, Denmark

Cisapride Versus Placebo for 8 Weeks on Glycemic Control and Gastric Emptying in Insulin-Dependent Diabetes: A Double Blind Cross-Over Trial1

1999 ◽  
Vol 84 (7) ◽  
pp. 2357-2362
Author(s):  
Georg Stacher ◽  
Guntram Schernthaner ◽  
Mario Francesconi ◽  
Hans-Peter Kopp ◽  
Helmar Bergmann ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Gastric Emptying ◽  
Glycemic Control ◽  
Autonomic Neuropathy ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Double Blind ◽  
Insulin Dependent

In insulin-dependent diabetes mellitus, slow gastric emptying may make absorption unpredictable and foster glycemic instability. Cisapride accelerates emptying, but controlled long term studies are scarce, and effects on glycemic control unknown. We investigated, in patients with insulin-dependent diabetes mellitus and unstable glycemia, the effects of 10 mg cisapride 4 times daily for 8 weeks vs. placebo on glycemic control and gastric emptying under random, cross-over, double blind conditions. In 14 patients with delayed and 9 with nondelayed emptying, blood glucose variability over 2 8-week treatment periods separated by a 4-week wash-out and gastric emptying of a semisolid 1168-kJ meal immediately after the treatment periods were assessed. Cisapride did not affect glycemic control [sd of within-patient mean blood glucose, 4.2 mmol/L ± 0.1 (±sem) vs. 4.0 ± 0.1 mmol/L after placebo; hemoglobin A1c, 8.3 ± 0.2% vs. 8.5 ± 0.2%]. Emptying was faster after cisapride than after placebo in 8 of 14 patients with delayed vs. 7 of 9 with nondelayed emptying (P = NS) and in 11 of 15 without vs. 4 of 8 with cardiovascular autonomic neuropathy (P = NS). Autonomic neuropathy prevailed in 7 of 14 patients with delayed and 1 of 9 with nondelayed emptying. Blood glucose immediately before and during assessment of emptying was unrelated to the emptying rate, whereas blood glucose increases over fasting levels were greater with faster emptying (P&lt; 0.002). In conclusion, cisapride’s effects were not different from those of placebo on glycemic control and gastric emptying, it did not differently affect patients with delayed vs. nondelayed emptying, and it slightly accelerated emptying (P = NS) in patients without, but not in those with, cardiovascular autonomic neuropathy. Blood glucose levels before and during assessment of emptying did not affect emptying, but the glucose rise over fasting levels was greater with faster emptying.

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