Role of KATP Channel Loss in Type 2 Diabetes

Conditions

• Obesity and Type 2 Diabetes

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Accepted

Interventions

• 10 mg glipizide ingestion — DRUG
  A single dose of 10 mg glipizide will be ingested

Study Details

Insulin is a hormone that is made by β-cells in the pancreas and when released into the bloodstream helps control blood sugar levels. Insulin release is regulated by electrical activity in the β-cell which is generated by the ATP-sensitive potassium (KATP) channel. While reduced KATP activity is associated with increased insulin secretion, animals lacking KATP exhibit reduced secretion. This crossover from hypersecretion to undersecretion with KATP loss mirrors insulin secretion during type 2 diabetes. Intriguingly, evidence from cell and animal models suggest that chronically stimulated β-cells can lose KATP revealing a possible role for KATP loss in the failure of insulin secretion and poor control of blood sugar observed in type 2 diabetes. This study will therefore examine insulin responses following ingestion of a single dose of a sulfonylurea called glipizide that inhibits KATP channels in people with and without type 2 diabetes. The goal is to determine whether KATP channel activity is reduced during type 2 diabetes progression.

Key Dates

Start date

Mar 7, 2025

Status verified

Jul 2025

Primary completion

Mar 31, 2026

Completion

Jul 1, 2026

Study Design

Enrollment

40 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: Lean with normal glucose tolerance
  Body mass index ≥18.5 and \<25.0 kg/m², fasting plasma glucose concentration \<95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
• Experimental: Obesity with normal glucose tolerance
  Body mass index ≥30 and \<50 kg/m², fasting plasma glucose concentration \<95 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
• Experimental: Obesity with impaired fasting glucose
  Body mass index ≥30 and \<50 kg/m², fasting plasma glucose concentration 100-125 mg/dl, and 2-hr oral glucose tolerance test plasma glucose concentration \<200 mg/dl.
• Experimental: Obesity with type 2 diabetes
  Body mass index ≥30 and \<50 kg/m²; HbA1C 6.5-9.5%, fasting plasma glucose ≥126 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≥200 mg/dl and/or medical history of type 2 diabetes and currently using anti-diabetic medications.

Primary Outcome Measure

Insulin secretion [ Time Frame: 90 minutes after glipizide ingestion ]

Central Contacts

• Kyle Timmons
  314-273-1879
  [email protected]

Locations (1)

Find similar trials in St Louis, MO

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