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Diabetes Obes Metab. 2017 Sep;19(9):1267-1275. doi: 10.1111/dom.12952. Epub 2017 May 31.

Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

Author information

1
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
2
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, Virginia.

Abstract

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 and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1  min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp.

RESULTS:

Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion.

CONCLUSIONS:

These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.

KEYWORDS:

bariatric surgery; ghrelin; glucose metabolism; insulin resistance

PMID:
28345790
PMCID:
PMC5568950
DOI:
10.1111/dom.12952
[Indexed for MEDLINE]
Free PMC Article

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