Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery

September 8, 2025 updated by: The University of Texas Health Science Center at San Antonio

Hormonal and Neural Control of Insulin Secretion Following Gastric Bypass Surgery

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78207
        • Recruiting
        • Texas Diabetes Institute - University Health System
        • Principal Investigator:
          • Marzieh Salehi
        • Contact:
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • South Texas Veterans Health Care System
        • Contact:
        • Principal Investigator:
          • Marzieh Salehi, MD, MS
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Hypoglycemic RYGB patients with documented blood glucose level <50 mg/dl
  • Asymptomatic individuals with bariatric surgery
  • Healthy non-surgical patients with no personal history of diabetes
  • Subjects must physically be able to come to our clinical research center at Cedars-Sinai Medical Center

Exclusion Criteria:

  • Active heart, lung, liver, gastrointestinal or kidney disease; unable to give informed consent; pregnancy; uncontrolled high blood pressure or high cholesterol; significant anemia (hemoglobin <11g/dL); prisoners or institutionalized individuals; type 2 diabetes melitis; development of any serious medical or psychiatric illness during recruitment or studies;
  • RYGB patients will also be disqualified if they have gastric outlet obstruction or severe diarrhea
  • Healthy non-surgical patients with personal history of diabetes

For administration of atropine, the following exclusions also apply:

  • History of glaucoma
  • Uncontrolled hypertension (any subjects with BP>140/90 and history of dyslipidemia
  • Taking any medication that might interact with atropine and cannot be stopped will be excluded from the study)
  • Myasthenia gravis
  • Brain pathology
  • Enlarged prostate in men

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exendin-(9-39)
To evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
Drug: Exendin-(9-39)
A physiological study to evaluate the role of GLP-1 signaling in glucose tolerance and insulin secretion
Other Names:
  • No other name for Exendin-(9-39)
Experimental: atropine
To evaluate the effect of neural activation on insulin secretion and glucose metabolism
Drug: Atropine
A physiological study to evaluate the effect of neural activation on insulin secretion and glucose metabolism
Other Names:
  • Atropine sulfate
Experimental: GLP-1 and GIP
to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Drug: GLP-1 and GIP
A physiological study to evaluate the beta-cell sensitivity to different doses of exogenous gut hormones
Other Names:
  • No other names for GLP-1 and GIP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Gut hormones and neural signaling contribution to insulin secretion rate and glucose tolerance
Time Frame: Each study of the protocol is conducted up to seven hours with data collected at intervals specific to the individual study procedure.
Each study of the protocol is conducted up to seven hours with data collected at intervals specific to the individual study procedure.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center at San Antonio

Investigators

  • Principal Investigator: Marzieh Salehi, MD, MS, Marzieh Salehi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

October 7, 2009

First Submitted That Met QC Criteria

October 8, 2009

First Posted (Estimated)

October 9, 2009

Study Record Updates

Last Update Posted (Estimated)

September 9, 2025

Last Update Submitted That Met QC Criteria

September 8, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-070H
  • DK083554 (Other Grant/Funding Number: NIDDK)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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