Effect of Glutamate on Postprandial Glucose Excursion and Gastric Emptying of a Lipid-Containing Liquid Meal in Healthy Humans

Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1 was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

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Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.5.e981 ◽

1997 ◽

Vol 273 (5) ◽

pp. E981-E988 ◽

Cited By ~ 130

Author(s):

Michael A. Nauck ◽

Ulrich Niedereichholz ◽

Rainer Ettler ◽

Jens Juul Holst ◽

Cathrine Ørskov ◽

...

Keyword(s):

Gastric Emptying ◽

Normal Subjects ◽

Diabetic Patients ◽

Phenol Red ◽

Type 2 Diabetic Patients ◽

Liquid Meal ◽

Healthy Humans ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Insulin Responses

Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7—36) amide and GLP-1-(7—37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 ± 3 yr; body mass index 22.9 ± 1.6 kg/m2; hemoglobin A1C 5.0 ± 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7—36) amide (0.4, 0.8, or 1.2 pmol ⋅ kg−1 ⋅ min−1), GLP-1-(7—37) (1.2 pmol ⋅ kg−1 ⋅ min−1), or placebo was infused intravenously from −30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7—36) amide ( P < 0.0001). Effects of GLP-1-(7—37) at 1.2 pmol ⋅ kg−1 ⋅ min−1were virtually identical. GLP-1 dose dependently stimulated fasting insulin secretion (−30 to 0 min) and slightly reduced glucose concentrations. After the meal (0–240 min), integrated incremental glucose ( P < 0.0001) and insulin responses ( P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7—36) amide or -(7—37) inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol ⋅ kg−1 ⋅ min−1) still have a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7—36) amide and -(7—37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms).

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A Review of Recent Findings on Meal Sequence: An Attractive Dietary Approach to Prevention and Management of Type 2 Diabetes

Nutrients ◽

10.3390/nu12092502 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2502 ◽

Cited By ~ 1

Author(s):

Sodai Kubota ◽

Yanyan Liu ◽

Katsumi Iizuka ◽

Hitoshi Kuwata ◽

Yutaka Seino ◽

...

Keyword(s):

Body Weight ◽

Dietary Fiber ◽

Saturated Fatty Acids ◽

Postprandial Glucose ◽

Simple Method ◽

Glucose Excursion ◽

Dietary Fiber Intake ◽

Metabolic Conditions ◽

Postprandial Glucose Excursion ◽

Diabetes And Obesity

While adjustment of total energy and nutritional balance is critically important, meal sequence, a relatively simple method of correcting postprandial hyperglycemia, is becoming established as a practical dietary approach for prevention and management of diabetes and obesity. Meal sequence, i.e., consumption of protein and/or fat before carbohydrate, promotes secretion of glucagon-like peptide-1 (GLP-1) from the gut and ameliorates secretions of insulin and glucagon and delays gastric emptying, thereby improving postprandial glucose excursion. GLP-1 is known to suppress appetite by acting on the hypothalamus via the afferent vagus nerve. Thus, enhancement of GLP-1 secretion by meal sequence is expected to reduce body weight. Importantly, consumption of a diet rich in saturated fatty acids such as meat dishes before carbohydrate increases secretions of not only GLP-1 but also glucose-dependent insulinotropic polypeptide (GIP), which promotes energy storage in adipose tissue and may lead to weight gain in the long term. Dietary fiber intake before carbohydrate intake significantly reduces postprandial glucose elevation and may have a weight loss effect, but this dietary strategy does not enhance the secretion of GLP-1. Thus, it is suggested that their combination may have additive effects on postprandial glucose excursion and body weight. Indeed, results of some clinical research supports the idea that ingesting dietary fiber together with meal sequence of protein and/or fat before carbohydrate benefits metabolic conditions of individuals with diabetes and obesity.

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Effects of Fuscoporia obliqua on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients

Journal of Traditional Chinese Medicine ◽

10.1016/s0254-6272(08)60014-x ◽

2008 ◽

Vol 28 (1) ◽

pp. 49-57 ◽

Cited By ~ 2

Author(s):

Toshihiro Maenaka ◽

Masami Oshima ◽

Yuka Itokawa ◽

Takashi Masubuchi ◽

Yasuyuki Takagi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Postprandial Glucose ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Glucose Excursion ◽

Postprandial Glucose Excursion ◽

Type 2 Diabetic

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Postmeal exercise blunts postprandial glucose excursions in people on metformin monotherapy

Journal of Applied Physiology ◽

10.1152/japplphysiol.00213.2017 ◽

2017 ◽

Vol 123 (2) ◽

pp. 444-450 ◽

Cited By ~ 12

Author(s):

Melissa L. Erickson ◽

Jonathan P. Little ◽

Jennifer L. Gay ◽

Kevin K. McCully ◽

Nathan T. Jenkins

Keyword(s):

Time Window ◽

Glucose Monitoring ◽

Area Under The Curve ◽

Postprandial Glucose ◽

Interactive Effects ◽

Moderate Intensity ◽

Glucose Excursion ◽

Metformin Monotherapy ◽

Physiological Outcomes ◽

Postprandial Glucose Excursion

Metformin is used clinically to reduce fasting glucose with minimal effects on postprandial glucose. Postmeal exercise reduces postprandial glucose and may offer additional glucose-lowering benefit beyond that of metformin alone, yet controversy exists surrounding exercise and metformin interactions. It is currently unknown how postmeal exercise and metformin monotherapy in combination will affect postprandial glucose. Thus, we examined the independent and combined effects of postmeal exercise and metformin monotherapy on postprandial glucose. A randomized crossover design was used to assess the influence of postmeal exercise on postprandial glucose excursions in 10 people treated with metformin monotherapy (57 ± 10 yr, HbA1C = 6.3 ± 0.6%). Each participant completed the following four conditions: sedentary and postmeal exercise (5 × 10-min bouts of treadmill walking at 60% V̇o2max) with metformin and sedentary and postmeal exercise without metformin. Peak postprandial glucose within a 2-h time window and 2-h total area under the curve was assessed after a standardized breakfast meal, using continuous glucose monitoring. Postmeal exercise significantly blunted 2-h peak ( P = 0.001) and 2-h area under the curve ( P = 0.006), with the lowest peak postprandial glucose excursion observed with postmeal exercise and metformin combined ( P < 0.05 vs. all other conditions: metformin/sedentary: 12 ± 3.4, metformin/exercise: 9.7 ± 2.3, washout/sedentary: 13.3 ± 3.2, washout/exercise: 11.1 ± 3.4 mmol/l). Postmeal exercise and metformin in combination resulted in the lowest peak postprandial glucose excursion compared with either treatment modality alone. Exercise timed to the postprandial phase may be important for optimizing glucose control during metformin monotherapy. NEW & NOTEWORTHY The interactive effects of metformin and exercise on key physiological outcomes remain an area of controversy. Findings from this study show that the combination of metformin monotherapy and moderate-intensity postmeal exercise led to beneficial reductions in postprandial glucose excursions. Postmeal exercise may be a useful strategy for the management of postprandial glucose in people on metformin.

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