Effects of Intravenous Glucagon-Like Peptide-1 on Gastric Emptying and Intragastric Distribution in Healthy Subjects: Relationships with Postprandial Glycemic and Insulinemic Responses

Little, Tanya J.; Pilichiewicz, Amelia N.; Russo, Antonietta; Phillips, Liza K.; Jones, Karen L.; Nauck, Michael A.; Wishart, Judith M.; Feinle‐Bisset, Christine

doi:10.1210/jc.2005-2220

Cited by 174 publications

(149 citation statements)

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“…The observed acceleration in GE may be an underestimate given that acute hyperglycaemia slows GE [40]. The acute slowing of GE by exogenous GLP-1 is substantial [17][18][19], as we confirmed, so that the consequent reduction in glucose may be associated with a reduction, rather than an increase, in insulin [17][18][19]. While blood glucose levels were lower during the GLP-1 infusion than the control infusion, the overall glycaemic profile was predictably greater in patients with type 2 diabetes.…”

Section: Discussionsupporting

confidence: 64%

“…GE in healthy individuals exhibits a wide interindividual variation of~4-17 kJ/min (~1-4 kcal/min) [14]; this is increased in diabetes because of the high prevalence of delayed [15], and occasionally rapid, GE [16]. The reduction in postprandial glucose following acute administration of GLP-1 [17][18][19] or 'short-acting' GLP-1 agonists [20,21] relates primarily to slowing of GE but clinical studies relating to the effects of GLP-1 and its agonists on BP have not discriminated between effects on fasting vs postprandial BP.…”

Section: Introductionmentioning

confidence: 99%

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Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

et al. 2015

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Aims/hypothesis A postprandial fall in BP occurs frequently in older individuals and in patients with type 2 diabetes. The magnitude of this decrease in BP is related to the rate of gastric emptying (GE). Intravenous administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal glucose in healthy older individuals. We sought to determine the effects of exogenous GLP-1 on BP, GE, superior mesenteric artery (SMA) flow and glycaemic response to oral ingestion of glucose in healthy older individuals and patients with type 2 diabetes. Methods Fourteen older volunteers (six men, eight women; age 72.1±1.1 years) and ten patients with type 2 diabetes (six men, four women; age 68.7±3.4 years; HbA 1c 6.6±0.2% [48.5± 2.0 mmol/mol]; nine with blood glucose managed with metformin, two with a sulfonylurea and one with a dipeptidyl-peptidase 4 inhibitor) received an i.v. infusion of GLP-1 (0.9 pmol kg −1 min −1 ) or saline (154 mmol/l NaCl) for 150 min (t=−30 min to t= 120 min) in randomised order. At t=0 min, volunteers consumed a radiolabelled 75 g glucose drink. BP was assessed with an automated device, GE by scintigraphy and SMA flow by ultrasonography. Blood glucose and serum insulin were measured. Results GLP-1 attenuated the fall in diastolic BP after the glucose drink in older individuals (p<0.05) and attenuated the fall in systolic and diastolic BP in patients with type 2 diabetes (p<0.05). GE was faster in patients with type 2 diabetes than in healthy individuals (p<0.05). In both groups, individuals had slower GE (p<0.001), decreased SMA flow (p<0.05) and a lower degree of glycaemia (p<0.001) when receiving GLP-1. Conclusions/interpretation Intravenous GLP-1 attenuates the hypotensive response to orally administered glucose and decreases SMA flow, probably by slowing GE. GLP-1 and 'short-acting' GLP-1 agonists may be useful in the management of postprandial hypotension.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

et al. 2015

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“…Circulating GLP-1 levels rise aft er a meal and fall in the fasted state. GLP-1 reduces food intake (Parker et al 2013), suppresses glucagon secretion (Hare 2010), and delays gastric emptying (Little et al 2006).…”

Section: Role Of the Gastrointestinal Tract Peptidesmentioning

confidence: 99%

Central and peripheral control of food intake

Abdalla

2017

Endocrine Regulations

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Th e maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive. Th e body weight depends on the balance between the energy intake and energy expenditure. Increased food intake over the energy expenditure of prolonged time period results in an obesity. Th e obesity has become an important worldwide health problem, even at low levels. Th e obesity has an evil eff ect on the health and is associated with a shorter life expectancy. A complex of central and peripheral physiological signals is involved in the control of the food intake. Centrally, the food intake is controlled by the hypothalamus, the brainstem, and endocannabinoids and peripherally by the satiety and adiposity signals. Comprehension of the signals that control food intake and energy balance may open a new therapeutic approaches directed against the obesity and its associated complications, as is the insulin resistance and others. In conclusion, the present review summarizes the current knowledge about the complex system of the peripheral and central regulatory mechanisms of food intake and their potential therapeutic implications in the treatment of obesity. Th e maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive (Jequier and Tappy 1999). As a compensatory mechanism, hunger increases and energy expenditure decreases the weight loss. However, opposite responses are triggered when body weight increases. Body weight can change only when energy intake is not equal to energy expenditure over a given period of time (Bray et al. 2012). A complex physiological control system is involved in the maintenance of the energy balance. Th is system includes aff erent signals from the periphery about the state of the energy stores and eff erent signals that affect the energy intake and expenditure (Sandoval et al. 2008). Th is regulatory system is formed by multiple interactions between the gastrointestinal tract (GIT), adipose tissue, and the central nervous system (CNS). It is infl uenced by behavioral, sensorial, autonomic, nutritional, and endocrine mechanisms (Boguszewski et al. 2010). Satiety and adiposity signalsTh e food intake control includes a short-term regulation, which determines the beginning and the end of a meal (hunger and satiation) and the interval between the meals (satiety) and a long-term regulation with factors (signals of adiposity), which help to regulate the body energy depots (Cummings and Overduin 2007).Th e satiation means a suppression of the hunger and termination of the food intake aft er ingestion of Unauthenticated Download Date | 5/11/18 9:54 AM

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“…During fasting, exogenous GLP-1 and GLP-1 agonists lower plasma glucose primarily via effects on the islet cell to increase insulin and reduce glucagon secretion in a glucose-dependent manner (5,6), whereas during the postprandial phase, glucose lowering is predominantly mediated through their effect to slow gastric emptying (7,8). Accordingly, in healthy patients and in those with type 2 diabetes, postprandial insulin concentrations are suppressed, rather than stimulated, during GLP-1 administration (7,9). The magnitude of the deceleration of gastric emptying induced by exogenous GLP-1 and its agonists is dependent on the baseline rate of gastric emptying, so that the emptying rate is markedly slowed in those with relatively rapid gastric emptying before GLP-1 administration, whereas the rate is largely unaffected when gastric emptying is already delayed at baseline (10,11).…”

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confidence: 99%

Hyperglycemia Potentiates the Slowing of Gastric Emptying Induced by Exogenous GLP-1

et al. 2015

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OBJECTIVEAcute hyperglycemia markedly slows gastric emptying. Exogenous GLP-1 also slows gastric emptying, leading to diminished glycemic excursions. The primary objective was to determine whether hyperglycemia potentiates the slowing of gastric emptying induced by GLP-1 administration. RESEARCH DESIGN AND METHODSTen healthy participants were studied on 4 separate days. Blood glucose was clamped at hyperglycemia using an intravenous infusion of 25% dextrose (∼12 mmol/L; hyper) on 2 days, or maintained at euglycemia (∼6 mmol/L; eu) on 2 days, between t = 215 and 240 min. During hyperglycemic and euglycemic days, participants received intravenous GLP-1 (1.2 pmol/kg/min) and placebo in a randomized double-blind fashion. At t = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq technetium-99m-sulfur colloid and 3 g 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from t = 0 to 240 min and serum 3-OMG taken at regular intervals from t = 15 to 240 min. The areas under the curve for gastric emptying and 3-OMG were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. RESULTSHyperglycemia slowed gastric emptying (eu/placebo vs. hyper/placebo; P < 0.001) as did GLP-1 (eu/placebo vs. eu/GLP-1; P < 0.001). There was an additive effect of GLP-1 and hyperglycemia, such that gastric emptying was markedly slower compared with GLP-1 administration during euglycemia (eu/GLP-1 vs. hyper/GLP-1; P < 0.01). CONCLUSIONSAcute administration of exogenous GLP-1 profoundly slows gastric emptying during hyperglycemia in excess of the slowing induced by GLP-1 during euglycemia. Studies are required to determine the effects of hyperglycemia on gastric emptying with the subcutaneously administered commercially available GLP-1 agonists in patients with type 2 diabetes.Gastric emptying is a major determinant of postprandial glycemia in health, as well as in type 1 and type 2 diabetes (1,2), and accounts for ;35% of the variance in the initial glycemic response to oral carbohydrate (1). Accordingly, dietary and pharmacological strategies that slow gastric emptying, including short-acting GLP-1 agonists, are useful interventions to attenuate postprandial glycemic excursions and overall glycemia in type 2 diabetes (3).

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Effects of Intravenous Glucagon-Like Peptide-1 on Gastric Emptying and Intragastric Distribution in Healthy Subjects: Relationships with Postprandial Glycemic and Insulinemic Responses

Cited by 174 publications

References 37 publications

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

Central and peripheral control of food intake

Hyperglycemia Potentiates the Slowing of Gastric Emptying Induced by Exogenous GLP-1

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