Gut ghrelin regulates hepatic glucose production and insulin signaling via a gut-brain-liver pathway.

Lin Y, Liang Z, He L, Yang M, Liu D, Gu HF, Liu H, Zhu Z, Zheng H, Li L, Yang G

Cell communication and signaling : CCS25 Jan 2019Cited by 21 (Europe PMC)

PMID30683114PMCIDPMC6347823DOI10.1186/s12964-019-0321-yPepBankPUB-30683114

Summary

BackgroundGhrelin modulates many physiological processes. However, the effects of intestinal ghrelin on hepatic glucose production (HGP) are still unclear. The current study was to explore the roles of intestinal ghrelin on glucose homeostasis and insulin signaling in the liver.MethodsThe system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-³H] glucose as a tracer were used to analyze the effect of intestinal ghrelin. Intraduodenal co-infusion of ghrelin, tetracaine and Activated Protein Kinase (AMPK) activator (AICAR), or pharmacologic and molecular inhibitor of N-methyl-D-aspartate receptors within the dorsal vagal complex, or hepatic vagotomy in rats were used to explore the possible mechanism of the effect of intestinal ghrelin on HGP.ResultsOur results demonstrated that gut infusion of ghrelin inhibited duodenal AMP-dependent protein kinase (AMPK) signal pathways, increased HGP and expression of gluconeogenic enzymes, and decreased insulin signaling in the liver of the rat. Intraduodenal co-infusion of ghrelin receptor antagonist [D-Lys³]-GHRP-6 and AMPK agonist with ghrelin diminished gut ghrelin-induced increase in HGP and decrease in glucose infusion rate (GIR) and hepatic insulin signaling. The effects of gut ghrelin were also negated by co-infusion with tetracaine, or MK801, an N-methyl-D-aspartate (NMDA) receptor inhibitor, and adenovirus expressing the shRNA of NR1 subunit of NMDA receptors (Ad-shNR1) within the dorsal vagal complex, and hepatic vagotomy in rats. When ghrelin and lipids were co-infused into the duodenum, the roles of gut lipids in increasing the rate of glucose infusion (GIR) and lowering HGP were reversed.ConclusionsThe current study provided evidence that intestinal ghrelin has an effect on HGP and identified a neural glucoregulatory function of gut ghrelin signaling.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking GHRP-6.

01AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In rats, interventions with D-Lys-GHRP‑6 and an AMPK agonist diminished the gut ghrelin-induced increase in hepatic glucose production.
In plain wordsIn rats, interventions with D-Lys-GHRP‑6 and an AMPK agonist reduced the rise in liver glucose production from gut ghrelin.
Peptide
GHRP-6
Outcome
DecreaseGhrelin-induced hepatic glucose production
Study
ratn: not reported in source
normal chow-diet rats with pancreatic-euglycemic clamp
Comparator
Gut ghrelin
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Intraduodenal co-infusion of ghrelin receptor antagonist [D-Lys³]-GHRP-6 and AMPK agonist with ghrelin diminished gut ghrelin-induced increase in HGP and decrease in glucose infusion rate (GIR) and hepatic insulin signaling.
1 context sentence(design, population, supporting numbers)
Summary · context
The system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-³H] glucose as a tracer were used to analyze the effect of intestinal ghrelin.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3068311401
02AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In rats, interventions with D-Lys-GHRP‑6 and an AMPK agonist diminished the gut ghrelin-induced decrease in glucose infusion rate.
In plain wordsIn rats, interventions with D-Lys-GHRP‑6 and an AMPK agonist reduced the fall in glucose infusion rate from gut ghrelin.
Peptide
GHRP-6
Outcome
IncreaseGhrelin-induced glucose infusion rate decrease
Study
ratn: not reported in source
normal chow-diet rats with pancreatic-euglycemic clamp
Comparator
Gut ghrelin
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Intraduodenal co-infusion of ghrelin receptor antagonist [D-Lys³]-GHRP-6 and AMPK agonist with ghrelin diminished gut ghrelin-induced increase in HGP and decrease in glucose infusion rate (GIR) and hepatic insulin signaling.
1 context sentence(design, population, supporting numbers)
Summary · context
The system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-³H] glucose as a tracer were used to analyze the effect of intestinal ghrelin.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3068311402
03AnimalNot a test of GHRP-6 aloneAnimal study (in vivo)Mechanism
In rats, interventions with D-Lys-GHRP‑6 and an AMPK agonist diminished the gut ghrelin-induced decrease in hepatic insulin signaling.
In plain wordsIn rats, interventions with D-Lys-GHRP‑6 and an AMPK agonist reduced the fall in liver insulin signaling from gut ghrelin.
Peptide
GHRP-6
Outcome
IncreaseGhrelin-induced hepatic insulin signaling decrease
Study
ratn: not reported in source
normal chow-diet rats with pancreatic-euglycemic clamp
Comparator
Gut ghrelin
Outcome group
Receptor activity and mechanism · Liver
Source sentences
Summary
Intraduodenal co-infusion of ghrelin receptor antagonist [D-Lys³]-GHRP-6 and AMPK agonist with ghrelin diminished gut ghrelin-induced increase in HGP and decrease in glucose infusion rate (GIR) and hepatic insulin signaling.
1 context sentence(design, population, supporting numbers)
Summary · context
The system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-³H] glucose as a tracer were used to analyze the effect of intestinal ghrelin.
In this study, GHRP-6 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking GHRP-6.
Show in the study text Report a problemFND-3068311403

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

Subjects

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