NCT01729299

Ghrelin Effect on Beta Cell Function in Health and Disease

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: David Dalessio · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

To determine the role of nutrient status on ghrelin regulation of insulin secretion. We hypothesize that ghrelin and glucagon-like peptide-1 (GLP-1)(both are hormones made in the gut,) have differential effects on β-cell function in the fed state. We will compare insulin secretion and glucose turnover during meal ingestion using a dual glucose tracer and mixed meal protocol in subjects receiving ghrelin or saline. We will also determine the role of ghrelin-stimulated GLP-1 levels in this process using the GLP-1 receptor (GLP-1R) antagonist Exendin(9-39) (Ex-9).

Detailed description

We plan to study 20 healthy subjects on 4 occasions where they will receive ghrelin, ghrelin+Ex-9, Ex-9 or saline infusion after an overnight fast in a randomized order; Ex-9 will be used to block GLP-1 action. A 240-minute meal tolerance test (MTT) using a dual glucose tracer method will serve as the foundation of each study visit. One tracer, \[6,6-2H2\]glucose will be infused intravenously before and during the test meal to quantify fasting endogenous glucose production (EGP), and glucose disappearance during the meal. A second tracer, \[U-13C\]glucose, will be included in the meal to trace the appearance of oral glucose. The systemic appearance rates of both ingested tracer and total (i.e., ingested and endogenously produced) glucose will be calculated. Using this protocol, we will be able to evaluate a) insulin secretion in response to mixed-meal ingestion, b) glucose appearance and glucose disappearance during meal ingestion, c) the ghrelin effect on these parameters without GLP-1, and d) the effect of GLP-1 in the response based on the effects with and without Ex-9. This dual-tracer method has been used to assess the ability of an individual to dispose of an oral glucose load, and accurately fractionates the appearance of ingested glucose in plasma (Ra meal), EGP, and peripheral glucose disposal (Rd) in this setting 41-42. The \[6,6-2H2\]glucose and \[U-13C\]glucose are stable-isotope tracers and are different from radioactive-isotope tracers in that they do not emit radiation. All procedures will be performed at the CTRC at the Cincinnati Children's Hospital Medical Center (CCHMC).

Conditions

• Diabetes

Interventions

Type	Name	Description
DRUG	Exendin (9-39)
DRUG	acyl ghrelin
DRUG	saline

Timeline

• Start date: 2013-04-01
• Primary completion: 2014-04-01
• Completion: 2014-04-01
• First posted: 2012-11-20
• Last updated: 2013-04-04

Locations

2 sites across 1 country: United States