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Interaction of GLP-1 and Ghrelin on Glucose Tolerance in Healthy Humans

Published on Oct 1, 2018in Diabetes7.20
· DOI :10.2337/db18-0451
Laura C. Page2
Estimated H-index: 2
(Duke University),
Amalia Gastaldelli64
Estimated H-index: 64
(National Research Council)
+ 2 AuthorsJenny Tong32
Estimated H-index: 32
(UC: University of Cincinnati)
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Abstract
Emerging evidence supports the importance of ghrelin to defend against starvation-induced hypoglycemia. This effect may be mediated by inhibition of glucose-stimulated insulin secretion as well as reduced insulin sensitivity. However, administration of ghrelin during meal consumption also stimulates the release of glucagon-like peptide 1 (GLP-1), an incretin important in nutrient disposition. The objective of this study was to evaluate the interaction between ghrelin and GLP-1 on parameters of glucose tolerance following a mixed-nutrient meal. Fifteen healthy men and women completed the study. Each consumed a standard meal on four separate occasions with a superimposed infusion of 1 ) saline, 2 ) ghrelin, 3 ) the GLP-1 receptor antagonist exendin(9-39) (Ex9), or 4 ) combined ghrelin and Ex9. Similar to previous studies, infusion of ghrelin caused glucose intolerance, whereas Ex9 had a minimal effect. However, combined ghrelin and Ex9 resulted in greater postprandial glycemia than either alone, and this effect was associated with impaired β-cell function and decreased glucose clearance. These findings suggest that in the fed state, stimulation of GLP-1 mitigates some of the effect of ghrelin on glucose tolerance. This novel interaction between gastrointestinal hormones suggests a system that balances insulin secretion and glucose disposal in the fed and fasting states.
  • References (48)
  • Citations (4)
Cite
References48
Newest
Published on Dec 1, 2017in Scientific Reports4.01
Hideyoshi Kaga3
Estimated H-index: 3
(Juntendo University),
Yoshifumi Tamura19
Estimated H-index: 19
(Juntendo University)
+ 11 AuthorsShigeki Aoki48
Estimated H-index: 48
(Juntendo University)
Hyperinsulinemia observed in obese subject is caused at least in part by low metabolic clearance rate of insulin (MCRI). However, the determinants of MCRI in non-obese subjects are not fully understood. To investigate the correlates of MCRI in healthy non-obese men (BMI <25 kg/m2), we studied 49 non-obese Japanese men free of cardiometabolic risk factors. Using a 2-step hyperinsulinemic euglycemic clamp, we evaluated MCRI and insulin sensitivity. We also calculated the rate of glucose disappeara...
Published on Sep 1, 2017in Diabetes, Obesity and Metabolism6.13
Robyn A. Tamboli12
Estimated H-index: 12
(VUMC: Vanderbilt University Medical Center),
Joseph Antoun3
Estimated H-index: 3
(VUMC: Vanderbilt University Medical Center)
+ 8 AuthorsVance L. Albaugh9
Estimated H-index: 9
(VUMC: Vanderbilt University Medical Center)
Aims Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). Materials and methods We assessed central a...
Published on May 1, 2017in Scientific Reports4.01
Esben Thyssen Vestergaard17
Estimated H-index: 17
,
Niels Jessen31
Estimated H-index: 31
+ 1 AuthorsJens Otto Lunde Jørgensen67
Estimated H-index: 67
Acyl Ghrelin Induces Insulin Resistance Independently of GH, Cortisol, and Free Fatty Acids
Published on Oct 1, 2016in Diabetologia7.11
Alice E. Adriaenssens5
Estimated H-index: 5
,
Berit Svendsen14
Estimated H-index: 14
(UCPH: University of Copenhagen)
+ 4 AuthorsFiona M. Gribble60
Estimated H-index: 60
Aims/hypothesis Intra-islet and gut–islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells.
Published on Jul 1, 2016in Molecular metabolism6.18
Michael R. DiGruccio9
Estimated H-index: 9
(UMN: University of Minnesota),
Alex M. Mawla3
Estimated H-index: 3
(UMN: University of Minnesota)
+ 5 AuthorsMark O. Huising31
Estimated H-index: 31
(UMN: University of Minnesota)
Abstract Objective Complex local crosstalk amongst endocrine cells within the islet ensures tight coordination of their endocrine output. This is illustrated by the recent demonstration that the negative feedback control by delta cells within pancreatic islets determines the homeostatic set-point for plasma glucose during mouse postnatal development. However, the close association of islet endocrine cells that facilitates paracrine crosstalk also complicates the distinction between effects media...
Published on Jun 1, 2016in The Journal of Clinical Endocrinology and Metabolism5.61
Jenny Tong32
Estimated H-index: 32
(UC: University of Cincinnati),
Harold W. Davis16
Estimated H-index: 16
(UC: University of Cincinnati)
+ 1 AuthorsDavid A. D'Alessio61
Estimated H-index: 61
(UC: University of Cincinnati)
Objectives: Administration of ghrelin inhibits the acute insulin response to glucose and worsens IV glucose tolerance in healthy subjects. Evidence from preclinical studies suggests that ghrelin may have differential effects on glucose metabolism during fasting and feeding. Our objective was to test the effects of ghrelin on glucose and insulin responses during a meal tolerance test. Design: Acyl ghrelin (0.26 and 2.0 μg/kg/h) or saline was infused in 13 healthy subjects on three separate occasi...
Published on Jun 1, 2016in Diabetes7.20
David Polidori25
Estimated H-index: 25
(Janssen Pharmaceutica),
Richard N. Bergman103
Estimated H-index: 103
(Cedars-Sinai Medical Center)
+ 1 AuthorsAnne E. Sumner28
Estimated H-index: 28
(NIH: National Institutes of Health)
Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin...
Published on May 1, 2015in Diabetes7.20
Jeffrey Gagnon2
Estimated H-index: 2
(U of T: University of Toronto),
Laurie L. Baggio33
Estimated H-index: 33
(U of T: University of Toronto)
+ 1 AuthorsPatricia L. Brubaker56
Estimated H-index: 56
(U of T: University of Toronto)
GLP-1 is a gastrointestinal L-cell hormone that enhances glucose-stimulated insulin secretion. Hence, strategies that prevent GLP-1 degradation or activate the GLP-1 receptor are used to treat patients with type 2 diabetes. GLP-1 secretion occurs after a meal and is partly regulated by other circulating hormones. Ghrelin is a stomach-derived hormone that plays a key role in whole-body energy metabolism. Because ghrelin levels peak immediately before mealtimes, we hypothesized that ghrelin plays ...
Published on Mar 2, 2015in Journal of Clinical Investigation12.28
Arianna Psichas5
Estimated H-index: 5
,
Frank Reimann56
Estimated H-index: 56
,
Fiona M. Gribble60
Estimated H-index: 60
The enteroendocrine system is the primary sensor of ingested nutrients and is responsible for secreting an array of gut hormones, which modulate multiple physiological responses including gastrointestinal motility and secretion, glucose homeostasis, and appetite. This Review provides an up-to-date synopsis of the molecular mechanisms underlying enteroendocrine nutrient sensing and highlights our current understanding of the neuro-hormonal regulation of gut hormone secretion, including the intera...
Yuanyuan Zhang2
Estimated H-index: 2
(UTSW: University of Texas Southwestern Medical Center),
Fei Fang1
Estimated H-index: 1
(UTSW: University of Texas Southwestern Medical Center)
+ 2 AuthorsTong-Jin Zhao16
Estimated H-index: 16
(UTSW: University of Texas Southwestern Medical Center)
Famine kills millions of people each year. Survival requires the maintenance of blood glucose. Famine depletes body fat, thereby removing a source of energy for hepatic glucose production. Here we used a mouse model of fat depletion to show that growth hormone (GH) maintains blood sugar by stimulating hepatic autophagy, the process by which the liver digests its organelles to provide energy and substrates for producing glucose. When fat-depleted mice are fasted, their stomachs secrete ghrelin, a...
Cited By4
Newest
Published on Apr 3, 2019in Journal of Neuroendocrinology3.04
Jenny Tong32
Estimated H-index: 32
(Duke University),
Sarah M. Gray3
Estimated H-index: 3
(Duke University),
Laura C. Page2
Estimated H-index: 2
(Duke University)
Published on Feb 1, 2019in Journal of Cystic Fibrosis4.29
Xingshen Sun15
Estimated H-index: 15
(UI: University of Iowa),
Yaling Yi12
Estimated H-index: 12
(UI: University of Iowa)
+ 8 AuthorsJohn F. Engelhardt76
Estimated H-index: 76
(UI: University of Iowa)
Abstract Background Insulin secretion is insufficient in cystic fibrosis (CF), even before diabetes is present, though the mechanisms involved remain unclear. Acyl-ghrelin (AG) can diminish insulin secretion and is elevated in humans with CF. Methods We tested the hypothesis that elevated AG contributes to reduced insulin secretion and hyperglycemia in CF ferrets. Results Fasting AG was elevated in CF versus non-CF ferrets. Similar to its effects in other species, AG administration in non-CF fer...
Published on May 1, 2019in Endocrinology3.80
Bharath K. Mani12
Estimated H-index: 12
(UTSW: University of Texas Southwestern Medical Center),
Kripa Shankar1
Estimated H-index: 1
(UTSW: University of Texas Southwestern Medical Center),
Jeffrey M. Zigman44
Estimated H-index: 44
(UTSW: University of Texas Southwestern Medical Center)
View next paperChronic administration of ghrelin regulates plasma glucose and normalizes insulin levels following fasting hyperglycemia and hyperinsulinemia.