Plasma Insulin Response to Oral and Intravenous Glucose Administration1

Elrick, Harold; Stimmler, L.; Hlad, C. J.; Arai, Y.

doi:10.1210/jcem-24-10-1076

Cited by 765 publications

(353 citation statements)

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“…I nsulin secretion after meal ingestion is stimulated not only by the rise in glycemia, but also by the secretion of peptide hormones ("incretins") from the gut (1,2). The postprandial enhancement of insulin secretion by gut-derived factors is called the incretin effect (2,3).…”

mentioning

confidence: 99%

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

et al. 2005

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Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses. Therefore, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 ؎ 4 years, BMI 25.0 ؎ 4.9 kg/m 2 ) were studied with an infusion of GLP-1 (0.8 pmol ⅐ kg ؊1 ⅐ min ؊1 from ؊30 to 240 min) or placebo. On separate occasions, the prokinetic drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at ؊30 min per oral), or erythromycin (200 mg intravenously from ؊30 to ؊15 min) were administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed amino acids in 400 ml) was administered at 0 min. Capillary and venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol red dilution technique. Statistical analyses were performed using repeated-measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the velocity of gastric emptying (P < 0.001). This was completely counterbalanced by erythromycin, whereas the other prokinetic drugs used had no effect. Postprandial glucose concentrations were lowered by GLP-1 (P < 0.001 vs. placebo), but this effect was partially reversed by erythromycin (P < 0.05). Insulin secretory responses to the meal were lower during GLP-1 administration (P < 0.05 vs. placebo). However, when erythromycin was added to GLP-1, insulin concentrations were similar to those in placebo experiments. The suppression of meal-related increments in glucagon secretion by GLP-1 was reversed by erythromycin (P < 0.001). The time course of GIP secretion was delayed during GLP-1 administration (P < 0.05), but when erythromycin was added, the pattern was similar to placebo experiments. GLP-1 administration led to a reduction in pancreatic polypeptide plasma concentrations (P < 0.05). In contrast, pancreatic polypeptide levels were markedly increased by erythromycin (P < 0.001). Intravenous erythromycin counteracts the deceleration of gastric emptying caused by GLP-1, probably by interacting with the parasympathetic nervous system (pancreatic polypeptide responses). Despite augmented rises in insulin secretion, the glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1. Diabetes 54: 2212-2218, 2005 I nsulin secretion after meal ingestion is stimulated not only by the rise in glycemia, but also by the secretion of peptide hormones ("incretins") from the gut (1,2). The postprandial enhancement of insulin secretion by gut-derived factors is called the ...

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confidence: 99%

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

et al. 2005

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“…This finding might be explained by drainage of the transplanted pancreas into the systemic circulation instead of the portal vein. The magnitude of the enteral stimulus, i. e. the incretin effect on insulin secretion during OGTT was unchanged after transplantation, suggesting that the incretin effect is not mediated by neural influences upon the endocrine pancreas.Key words: Glucose, incretin, insulin secretion, pancreatic transplantation, pigs.Oral glucose induces an insulin response more than twice as large as that induced by intravenous glucose [1][2][3][4]. The mechanism behind this phenomenon, termed incretin [5], has received much attention, but its nature has not yet been entirely explained.…”

mentioning

confidence: 99%

“…Oral glucose induces an insulin response more than twice as large as that induced by intravenous glucose [1][2][3][4]. The mechanism behind this phenomenon, termed incretin [5], has received much attention, but its nature has not yet been entirely explained.…”

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confidence: 99%

The enteral insulin-stimulation after pancreas transplantation in the pig

1976

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Summary. The insulin responses to an oral glucose tolerance test (OGTT) and in intravenous glucose infusion (IVGI), designed to copy the changes in serum glucose concentrations found during OGTT, were measured in four pigs before and after heterotopic pancreatico-duodenal allotransplantation and total pancreatectomy. After transplantation and total pancreatectomy a remarkable hyperinsulinaemia occurred during OGTT and IVGI, reflected by an almost two-fold increment in the insulinogenic index after transplantation. This finding might be explained by drainage of the transplanted pancreas into the systemic circulation instead of the portal vein. The magnitude of the enteral stimulus, i. e. the incretin effect on insulin secretion during OGTT was unchanged after transplantation, suggesting that the incretin effect is not mediated by neural influences upon the endocrine pancreas.Key words: Glucose, incretin, insulin secretion, pancreatic transplantation, pigs.Oral glucose induces an insulin response more than twice as large as that induced by intravenous glucose [1][2][3][4]. The mechanism behind this phenomenon, termed incretin [5], has received much attention, but its nature has not yet been entirely explained. The incretin effect has mainly been conceived as being of hormonal nature [6][7][8][9][10][11]. However, it might also be due to neural augmentation of the insulin response [4,[12][13][14], though until now no studies have excluded this possibility.The present study was designed to evaluate the necessity of pancreatic innervation on the incretin effect in pigs by studying the effect of heterotopic pancreatic allotransplantation on the insulin responses to oral and intravenous glucose administration. Material and MethodsEight healthy pigs of Danish Landrace weighing 29-34 kg were used in the study.The operative procedure has been described in detail previously [15]. In short, total pancreaticoduodenectomy was performed in the donor pig, with resection of an 8 cm long segment of aorta containing both the coeliac and the superior mesenteric arteries. In the recipient pigs pancreaticoduodenal transplantation was as follows: The infrarenal vena cava and the abdominal aorta were exposed for approximately 8 cm. The distal end of the donor aortic segment was anastomosed end-to-side to the abdominal aorta of the recipient and the donor portal vein joined end-to-side to the inferior vena cava of the recipient. The duodenal segment was anastomosed end-to-side to the upper part of jejtmum. Total Pan7 createctomy was performed in the recipient pig one week after transplantation. Penicillin was given during the first postoperative week. Immunosuppressive therapy was not given.The mean survival time of the four pigs was 73.5 days (range 35-98 days). They remained normoglycaemic for an average of 63.3 days (range 21-91 days). During the investigative period all pigs were in good clinical condition without any signs of malabsorptive disorders. After death the pigs were autopsied and, to insure that there were no remaining pa...

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“…23 In the 1960s, data suggested that enteral glucose elicited a much greater secretion of insulin than an isoglycemic amount of glucose administered intravenously. [36][37][38] This potentiation of insulin secretion by the gut was referred to as the intestinal secretion of insulin or incretin effect. The incretin effect is due to 2 enteroendocrine hormones: glucose-dependent insulinotropic polypeptide (GIP) and GLP-1.…”

Section: Treating Type 2 Dm With Incretin Therapymentioning

confidence: 99%

Incorporating Incretin-Based Therapies Into Clinical Practice: Differences Between Glucagon-Like Peptide 1 Receptor Agonists and Dipeptidyl Peptidase 4 Inhibitors

Davidson

2010

Mayo Clinic Proceedings

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Plasma Insulin Response to Oral and Intravenous Glucose Administration1

Cited by 765 publications

References 9 publications

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

The enteral insulin-stimulation after pancreas transplantation in the pig

Incorporating Incretin-Based Therapies Into Clinical Practice: Differences Between Glucagon-Like Peptide 1 Receptor Agonists and Dipeptidyl Peptidase 4 Inhibitors

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