GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Gut ghrelin regulates hepatic glucose production and insulin signaling via a gut-brain-liver pathway.
Lin. Yao Y; Liang. Zerong Z; He. Liping L; Yang. Mengliu M; Liu. Dongfang D; Gu. Harvest F HF; Liu. Hua H; Zhu. Zhiming Z; Zheng. Hongting H; Li. Ling L; Yang. Gangyi G
Key Findings
- Direct gut infusion of ghrelin increases hepatic glucose production and reduces liver insulin signaling in rats.
- Gut ghrelin suppresses duodenal AMPK activity, and this suppression is necessary for the rise in glucose output.
- The glucose‑raising effect depends on NMDA receptors in the brainstem and the vagus nerve; blocking these pathways or using a ghrelin‑receptor antagonist stops the effect.
Practical Outcomes
- For biohackers using GHRP‑6 (a ghrelin‑stimulating peptide) to boost growth hormone, be aware it may also raise blood sugar and blunt insulin action, especially if taken on an empty stomach. Monitoring glucose levels and timing doses around meals, or pairing with AMPK‑activating strategies, could mitigate this effect, but more human data are needed.
Summary
The study shows that when ghrelin (the hormone that makes you feel hungry) is delivered straight into the gut of rats, it tells the liver to make more glucose and weakens the liver's response to insulin. This effect works through specific brain‑liver nerve pathways and can be blocked by stopping ghrelin receptors, activating AMPK, or interfering with NMDA receptors.
Abstract
Ghrelin 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. 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-<sup>3</sup>H] 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. Our 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-Lys<sup>3</sup>]-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. The current study provided evidence that intestinal ghrelin has an effect on HGP and identified a neural glucoregulatory function of gut ghrelin signaling.
Study Information
pubmed
2019
2019-01-25T00:00:00.000Z
10.1186/s12964-019-0321-y
19
50