Effects of Xenin-25 on Insulin Secretion and Gastric Emptying in Humans With and Without a Complete Truncal Vagotomy

Summary

Glucose-dependent Insulinotropic Polypeptide (GIP) and xenin-25 are peptide hormones produced/released from your intestines and help regulate blood sugar levels after you eat. We have previously performed studies in humans that measured the effects of xenin-25 and GIP (alone and together) on blood sugar levels. One study was conducted with an intravenous infusion of glucose but without ingestion of a meal. In this study, xenin-25 increased the effects of GIP on insulin secretion- but only in humans without type 2 diabetes mellitus (T2DM). A second study was conducted in conjunction with ingestion of a meal. In this study, xenin-25 reduced blood glucose levels by delaying gastric emptying and this effect was similar in humans with and without T2DM. A variety of studies that we have performed suggest that xenin-25 works by activating nerves. A specific nerve called the vagus nerve plays an important role in regulating insulin secretion. This study will determine if the vagus nerve (which was disrupted if you had a vagotomy) is needed for the effects of xenin-25 on insulin secretion and/or gastric emptying.

Conditions

• Does the Vagus Nerve Mediate the Effects of Xenin-25

Interventions

DRUG

Graded Glucose Infusion with Placebo

Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes.

DRUG

Graded Glucose Infusion with GIP Alone

Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes.

DRUG

Graded Glucose Infusion with xenin-25 alone

Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes.

DRUG

Graded Glucose Infusion with GIP plus xenin-25

Starting at 0 minutes, glucose infusion rates will be increased to 1, 2, 3, 4, 6, and 8 mg/kg/min every 40 minutes. Starting at 0 minutes, a primed-continuous intravenous infusion of GIP plus xenin-25 in saline containing 1% human albumin will continue for 240 minutes. The study is finished at 240 minutes.

DRUG

Meal Tolerance Test with Placebo

At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes.

DRUG

Meal Tolerance Test with xenin-25

At 0 minutes, a liquid mixed meal (Boost Plus) plus acetaminophen will be ingested. Starting at 0 minutes, a primed-continuous intravenous infusion of xenin-25 in saline containing 1% human albumin will continue for 300 minutes. The study is finished at 300 minutes.

Sponsors & Collaborators

• American Diabetes Association

  collaborator OTHER

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Burton M Wice, PhD · Washington University School of Medicine

• Dominic Reeds, MD · Washington University School of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-01-31

Primary Completion

2018-07-31

Completion

2018-07-31

Countries

• United States

Study Locations