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Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes

NCT ID: NCT04466618

Last Updated: 2023-12-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-15

Study Completion Date

2022-12-31

Brief Summary

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GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.

Detailed Description

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Accumulating evidence suggests that in rodents and humans GLP-1 is synthesized within islets and may act locally in a paracrine fashion. Indeed, mice with genetic loss of intra-islet GLP-1 exhibit decreased insulin secretion and impaired response to metabolic stressors. 'Pancreatic' GLP-1 may contribute to the effects of DPP-4 inhibitors in rodents and humans. Antagonism of GLP1R with exendin-9,39 during fasting impairs the islet cell response to an I.V. glucose challenge. Islet GLP-1 content is increased in T2DM and in islets from non-diabetic humans exposed to hyperglycemia and Free Fatty Acids. These observations imply that paracrine GLP-1 secretion supports islet function in the presence of glucolipotoxicity. In this experiment we will examine the role of endogenous GLP-1 secretion in people with and without T2DM and during β-cell stress induced by FFA elevation.

Conditions

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Healthy Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Saline

Saline infusion

Group Type PLACEBO_COMPARATOR

Saline

Intervention Type BIOLOGICAL

Saline infused during the study

Exendin-9,39

Exendin-9,39 infusion

Group Type ACTIVE_COMPARATOR

Exendin-9,39

Intervention Type BIOLOGICAL

Exendin-9,39 infused during the study

Saline + Intralipid/Heparin

Induction of acute insulin resistance during Saline infusion

Group Type ACTIVE_COMPARATOR

Saline + Intralipid/Heparin

Intervention Type BIOLOGICAL

Saline infused during acute insulin resistance

Exendin-9,39 + Intralipid/Heparin

Induction of acute insulin resistance during Exendin-9,39 infusion

Group Type ACTIVE_COMPARATOR

Exendin-9,39 + Intralipid/Heparin

Intervention Type BIOLOGICAL

Exendin-9,39 infused during acute insulin resistance

Interventions

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Saline

Saline infused during the study

Intervention Type BIOLOGICAL

Exendin-9,39

Exendin-9,39 infused during the study

Intervention Type BIOLOGICAL

Saline + Intralipid/Heparin

Saline infused during acute insulin resistance

Intervention Type BIOLOGICAL

Exendin-9,39 + Intralipid/Heparin

Exendin-9,39 infused during acute insulin resistance

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Weight-stable, non-diabetic subjects


* Weight-stable, diabetic subjects treated with diet and lifestyle alone or with metformin monotherapy

Exclusion Criteria

* Age \< 25 or \> 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
* HbA1c ≥ 6.5%
* Use of glucose-lowering agents.
* For female subjects: positive pregnancy test at the time of enrollment or study
* History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
* Active systemic illness or malignancy.
* Symptomatic macrovascular or microvascular disease.


* Age \< 25 or \> 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
* Use of any glucose-lowering agent other than metformin.
* 2 or more fasting glucose values \> 250mg/dl on medication or after medication withdrawal.
* Unwillingness or inability to withdraw medication for three weeks prior to, and for the duration of the study.
* For female subjects: positive pregnancy test at the time of enrollment or study
* History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
* Active systemic illness or malignancy.
* Symptomatic macrovascular or microvascular disease.
Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Adrian Vella

OTHER

Sponsor Role lead

Responsible Party

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Adrian Vella

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Adrian Vella

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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Welch AA, Farahani RA, Egan AM, Laurenti MC, Zeini M, Vella M, Bailey KR, Cobelli C, Dalla Man C, Matveyenko A, Vella A. Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans. J Clin Invest. 2023 Nov 15;133(22):e173495. doi: 10.1172/JCI173495.

Reference Type DERIVED
PMID: 37751301 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

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R01DK126206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-003993

Identifier Type: -

Identifier Source: org_study_id