The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans

Part of paid clinical trials in Rochester, Minnesota.

Sponsor
Mayo Clinic
Study ID
NCT06972407
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

  • Genetic Predisposition
  • Type2diabetes

Eligibility Criteria

Sex
ALL
Age
25 Years - 70 Years
Healthy Volunteers
Accepted

Interventions

  • Exendin 9-39 — BIOLOGICAL
    A competitive antagonist of the GLP-1 receptor
  • Saline — OTHER
    Saline infusion will serve as an inactive comparator

Study Details

The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. Common genetic variation in the TCF7L2 locus (T-allele at rs7903146) arguably confers the greatest genetic risk of T2DM. It is associated with α- and β-cell dysfunction. TCF7L2 (the product of TCF7L2) was first described as the transcription factor necessary for proglucagon expression in intestinal L-cells (which secrete GLP-1). This led to speculation that TCF7L2 confers risk of diabetes via changes in circulating GLP-1. This has turned out to not be the case. This raises the possibility that these diabetogenic effects are mediated via an inability of islet GLP-1 to adapt to rising glycemia. Therefore, this experiment will determine the contribution of islet GLP-1 to the functional abnormalities of the islet associated with the TCF7L2 locus.

Key Dates

Start date
Oct 1, 2026
Status verified
Jan 2026
Primary completion
Dec 31, 2028
Completion
Mar 1, 2029

Study Design

Enrollment
80 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Active Comparator: Exendin 9-39
    Exendin 9-39 will be infused during fasting and during a hyperglycemic clamp
  • Placebo Comparator: Saline
    Saline will be infused during fasting and during a hyperglycemic clamp

Primary Outcome Measure

Change in fasting glucose [ Time Frame: Change in average glucose concentration between -30 min and 0 min of each study day (saline day vs. exendin 9-39 day) ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Mayo Clinic in RochesterRochesterMinnesota55905-

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By research site
Mayo Clinic in Rochester· Rochester, MN

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