Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats

2005 ◽  
Vol 288 (6) ◽  
pp. R1695-R1706 ◽  
Author(s):  
Prasanth K. Chelikani ◽  
Alvin C. Haver ◽  
Roger D. Reidelberger
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Intravenous Infusion ◽  
Sham Feeding ◽  
Feeding Experiments ◽  
Intravenous Infusions ◽  
Inhibit Food Intake ◽  
Hormonal Signal ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1(7–36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5–170 pmol·kg−1·min−1) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol·kg−1·min−1 and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7–50 pmol·kg−1·min−1) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol·kg−1·min−1 and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5–50 pmol·kg−1·min−1) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.

scholarly journals Amylin receptor blockade stimulates food intake in rats

2004 ◽  
Vol 287 (3) ◽  
pp. R568-R574 ◽  
Author(s):  
Roger D. Reidelberger ◽  
Alvin C. Haver ◽  
Urban Arnelo ◽  
D. David Smith ◽  
Courtney S. Schaffert ◽  
...  
Keyword(s):  
Food Intake ◽  
Intravenous Infusion ◽  
Liquid Diet ◽  
Meal Size ◽  
Meal Frequency ◽  
Energy Reserves ◽  
Selective Blockade ◽  
Inhibit Food Intake ◽  
Hormonal Signal ◽  
The Brain

Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves. Amylin potently reduces food intake, body weight, and adiposity when administered systemically or into the brain. Whether selective blockade of endogenous amylin action increases food intake and adiposity remains to be clearly established. In the present study, the amylin receptor antagonist acetyl-[Asn30, Tyr32] sCT-( 8 – 32 ) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur. Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60–2,000 pmol·kg−1·min−1), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol·kg−1·min−1) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h). Infusions began just before dark onset. Food intake and meal patterns during the first 4 h of the dark period were determined from continuous computer recordings of changes in food bowl weight. Amylin inhibited food intake by ∼50%, and AC187 attenuated this response by ∼50%. AC187 dose-dependently stimulated food intake (maximal increases from 76 to 171%), whether administered alone or with an intragastric infusion of liquid diet. Amylin reduced mean meal size and meal frequency, AC187 attenuated these responses, and AC187 administration alone increased mean meal size and meal frequency. These results support the hypothesis that endogenous amylin plays an essential role in reducing meal size and increasing the postmeal interval of satiety.

scholarly journals Glucagon Like Peptide 1 and Evidence Around Diabetes Specific Nutrition

2019 ◽  
Vol 10 (2) ◽  
pp. 64-75
Author(s):  
ANSHU JOSHI ◽  
SAMEER RAO ◽  
GANESH KADHE
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Food Intake ◽  
Diabetes Management ◽  
Monounsaturated Fatty Acids ◽  
Complex Carbohydrate ◽  
Soluble Fibre ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

There has been significant research and development in pharmaco-therapeutic molecules for management of type 2 diabetes mellitus (T2DM). Diabetes specific nutrition intervention & newer incretin-based therapies have gained a lot of attention. Since incretins play an essential role in augmenting the post-prandial release of insulin, it is important to understand the science behind incretins and modulation of same by diabetic-specific nutrition (DSN). The purpose of this article is to summarize the available science around glucagon like peptide 1 (GLP-1) and the known role of nutrition, particularly diabetes specific nutrition. Literature published in PubMed, Google scholar and Embase were studied up to the end of August 2018. The key words of GLP-1, T2DM and Nutrients were used in different combinations. It was found that macronutrient aspects of DSN like complex carbohydrate, soluble fibre, proteins and high monounsaturated fatty acids augment GLP-1 secretion from intestinal L-cells. This may be attributed to insulin-trophic effects of DSN as well as its effects in causing deceleration in gastric emptying and reducing food intake. Hence, it was concluded that augmenting GLP-1 secretion in response to the intake of certain nutrients helps in modulating insulin secretion, metabolic homeostasis as well as decelerating gastric emptying and reducing food intake. DSN increases endogenous GLP-1 secretion which in turn improves insulin secretion and sensitivity. Thus, integrating DSN in mainstay diabetes management plans may result in better glycaemic and metabolic controls, particularly when GLP-1 based therapies are concurrently in use. Key Messages: DSN containing complex carbohydrate, soluble fibre, proteins and high monounsaturated fatty acids (MUFAs) augments GLP-1 secretion which in turn improves insulin secretion and sensitivity.

scholarly journals The Glucagon-Like Peptide-1 Receptor Agonist Oxyntomodulin Enhances β-Cell Function but Does Not Inhibit Gastric Emptying in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5670-5678 ◽  
Author(s):  
Adriano Maida ◽  
Julie A. Lovshin ◽  
Laurie L. Baggio ◽  
Daniel J. Drucker
Keyword(s):  
Blood Glucose ◽  
Amino Acid ◽  
Gastric Emptying ◽  
Food Intake ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Glucose Administration ◽  
Amino Acid Peptide ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The proglucagon gene gives rise to multiple peptides that play diverse roles in the control of energy intake, gut motility, and nutrient disposal. Glucagon-like peptide-1 (GLP-1), a 30-amino-acid peptide regulates glucose homeostasis via control of insulin and glucagon secretion and by inhibition of gastric emptying and food intake. Oxyntomodulin (OXM) a 37-amino-acid peptide also derived from the proglucagon gene, binds to both the glucagon and GLP-1 receptor (GLP-1R); however, a separate OXM receptor has not yet been identified. Here we show that OXM, like other GLP-1R agonists, stimulates cAMP formation and lowers blood glucose after both oral and ip glucose administration, actions that require a functional GLP-1R. OXM also directly stimulates insulin secretion from murine islets and INS-1 cells in a glucose- and GLP-1R-dependent manner. Moreover, OXM ameliorates hyperglycemia and significantly reduces apoptosis in murine β-cells after streptozotocin administration and directly reduces apoptosis in thapsigargin-treated INS-1 cells. Unexpectedly, OXM, but not the GLP-1R agonist exendin-4, increased plasma levels of insulin after oral glucose administration. Moreover, OXM administered at doses that potently lower blood glucose had no effect on inhibition of gastric emptying but reduced food intake in WT mice. Taken together, these findings illustrate that although structurally distinct proglucagon-derived peptides such as GLP-1 and OXM engage the GLP-1R, OXM mimics some but not all of the actions of GLP-1R agonists in vivo. These findings may have implications for therapeutic efforts using OXM as a long-acting GLP-1R agonist for the treatment of metabolic disorders.

Effects of gastric emptying on the postprandial ghrelin response

2006 ◽  
Vol 290 (2) ◽  
pp. E389-E395 ◽  
Author(s):  
Wendy A. M. Blom ◽  
Anne Lluch ◽  
Sophie Vinoy ◽  
Annette Stafleu ◽  
Robin van den Berg ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Intravenous Infusion ◽  
Indirect Measurement ◽  
Gastric Emptying Rate ◽  
Total Ghrelin ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Ghrelin Secretion ◽  
Single Blind

Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin response as well as the role of insulin and other hormones possibly mediating this response. Fifteen healthy men [BMI 21.6 kg/m2 (SD 1.9), age 20.5 yr (SD 2.5)] were studied in a single-blind, crossover design. Subjects received two treatments separated by 1 wk: 1) a dairy breakfast in combination with a 3-h intravenous infusion of glucagon-like peptide-1 (GLP-1), which delays gastric emptying, and 2) a dairy breakfast in combination with a 3-h intravenous infusion of saline. Blood samples were drawn before breakfast and during the infusion. Postprandial ghrelin (total) responses were lower following the saline infusion compared with the GLP-1 infusion ( P < 0.05). Acetaminophen concentrations, an indirect measurement of gastric emptying rate, were inversely correlated with total ghrelin concentrations (saline r = −0.76; 95% CI = −0.90, −0.49, GLP-1 r = −0.47; 95% CI = −0.76, −0.04). Ghrelin concentrations were only weakly correlated with insulin concentrations (saline r = −0.36; 95% CI = −0.69, 0.09; GLP- 1 r = −0.42; 95% CI = −0.73, 0.03), but strongly inversely correlated with GIP concentrations (saline r = −0.74; 95% CI= −0.89, −0.45; GLP-1 r = −0.63; 95% CI = −0.84, −0.27). In conclusion, our results support the hypothesis that ghrelin requires postgastric feedback, which may not be regulated through insulin. Conversely, our data suggest a role of glucose-dependent insulinotropic polypeptide in ghrelin secretion.

Comparative effects of amylin and cholecystokinin on food intake and gastric emptying in rats

2001 ◽  
Vol 280 (3) ◽  
pp. R605-R611 ◽  
Author(s):  
Roger D. Reidelberger ◽  
Urban Arnelo ◽  
Lars Granqvist ◽  
Johan Permert
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Intravenous Infusion ◽  
Physiological Importance ◽  
Hormonal Signal ◽  
Effective Doses ◽  
Pancreatic Peptide ◽  
Dose Dependent ◽  
The Brain

CCK is a physiological inhibitor of gastric emptying and food intake. The pancreatic peptide amylin exerts similar actions, yet its physiological importance is uncertain. Objectives were to compare the dose-dependent effects of intravenous infusion of amylin and CCK-8 on gastric emptying and food intake in rats, and to assess whether physiological doses of amylin are effective. Amylin and CCK-8 inhibited gastric emptying with mean effective doses (ED50s) of 3 and 35 pmol · kg−1 · min−1 and maximal inhibitions of 60 and 65%, respectively. Amylin and CCK-8 inhibited food intake with ED50s of 8 and 14 pmol · kg−1 · min−1 and maximal inhibitions of 78 and 69%, respectively. The minimal effective amylin dose for each effect was 1 pmol · kg−1 · min−1. Our previous work suggests that this dose increases plasma amylin by an amount comparable to that produced by a meal. These results support the hypothesis that amylin acts as a hormonal signal to the brain to inhibit gastric emptying and food intake and that amylin produces satiety in part through inhibition of gastric emptying.

Long-term metabolic benefits of exenatide in mice are mediated solely via the known glucagon-like peptide 1 receptor

2014 ◽  
Vol 306 (7) ◽  
pp. R490-R498 ◽  
Author(s):  
Krystyna Tatarkiewicz ◽  
Emmanuel J. Sablan ◽  
Clara J. Polizzi ◽  
Christiane Villescaz ◽  
David G. Parkes
Keyword(s):  
Body Weight ◽  
Gastric Emptying ◽  
Food Intake ◽  
High Fat Diet ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 receptors (GLP-1R) are expressed in multiple tissues and activation results in metabolic benefits including enhanced insulin secretion, slowed gastric emptying, suppressed food intake, and improved hepatic steatosis. Limited and inconclusive knowledge exists regarding whether the effects of chronic exposure to a GLP-1R agonist are solely mediated via this receptor. Therefore, we examined 3-mo dosing of exenatide in mice lacking a functional GLP-1R (Glp1r−/−). Exenatide (30 nmol·kg−1·day−1) was infused subcutaneously for 12 wk in Glp1r−/− and wild-type (Glp1r+/+) control mice fed a high-fat diet. Glycated hemoglobin A1c (HbA1c), plasma glucose, insulin, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight, food intake, terminal hepatic lipid content (HLC), and plasma exenatide levels were measured. At the end of the study, oral glucose tolerance test (OGTT) and rate of gastric emptying were assessed. Exenatide produced no significant changes in Glp1r−/− mice at study end. In contrast, exenatide decreased body weight, food intake, and glucose in Glp1r+/+ mice. When compared with vehicle, exenatide reduced insulin, OGTT glucose AUC0–2h, ALT, and HLC in Glp1r+/+ mice. Exenatide had no effect on plasma amylase or lipase levels. Exenatide concentrations were approximately eightfold higher in Glp1r−/− versus Glp1r+/+ mice after 12 wk of infusion, whereas renal function was similar. These data support the concept that exenatide requires a functional GLP-1R to exert chronic metabolic effects in mice, and that novel “GLP-1” receptors may not substantially contribute to these changes. Differential exenatide plasma levels in Glp1r+/+ versus Glp1r−/− mice suggest that GLP-1R may play an important role in plasma clearance of exenatide and potentially other GLP-1-related peptides.

scholarly journals Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

2004 ◽  
Vol 91 (3) ◽  
pp. 439-446 ◽  
Author(s):  
Erik Näslund ◽  
N. King ◽  
S. Mansten ◽  
N. Adner ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Emptying ◽  
Food Intake ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
Subcutaneous Injections ◽  
Subcutaneous Infusion ◽  
Continuous Subcutaneous Infusion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Recombinant glucagon-like peptide-1 (7–36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15% reduction in mean food intake per meal (P=0·02) after 5d treatment. A weight loss of 0·55 (sem 0·2) kg (P<0·05) was registered after 5d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0·001) and CSI (P<0·05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.

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