Role of KATP Channel Loss in Type 2 Diabetes

Description

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.

Conditions

Obesity and Type 2 Diabetes

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Study Overview

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Study Details

Study overview

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.

Hyperglycemia Induced Hyperexcitability: A Novel Role for KATP in the Progression of Type 2 Diabetes

Role of KATP Channel Loss in Type 2 Diabetes

Condition
Obesity and Type 2 Diabetes
Intervention / Treatment

-

Contacts and Locations

Saint Louis

Washington University in St. Louis, Saint Louis, Missouri, United States, 63110

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.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Lean-normoglycemic group (n=10): BMI ≥18.5 and \<25.0 kg/m², fasting plasma glucose concentration \<100 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140-mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
  • * Obesity-normoglycemic group (n=10): BMI ≥30 and \<50 kg/m², fasting plasma glucose concentration \<100 mg/dl, 2-hr oral glucose tolerance test plasma glucose concentration ≤140 mg/dl, and hemoglobin A1C (HbA1C) ≤5.6%.
  • * Obesity-impaired fasting glucose group (n=10): BMI ≥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.
  • * Obesity-type 2 diabetes group (n=10): BMI ≥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 T2DM and currently using anti-diabetic medications.
  • * Diabetes therapy with insulin at \>0.5 units/kg/day.
  • * Any change in diabetes medication in previous 3 months.
  • * Unstable weight (\>2% change during the last 2 months before entering the study).
  • * Evidence of significant organ system dysfunction or disease other than obesity and T2D.
  • * Regular use of tobacco products.
  • * Excessive consumption of alcohol (≥3 drinks/day for men and ≥2 drinks/day for women).
  • * Use of medications that are known to affect the study outcome measures (e.g., steroids, non-statin lipid-lowering medications) or increase the risk of study procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this study.
  • * Anemia (Hemoglobin \<10.0 g/dL).
  • * Pregnant or breastfeeding.
  • * Unable or unwilling to follow the study protocol or for any reason the research team believes the volunteer is not an appropriate candidate for this study, including non-compliance with screening appointments or previous medical visits.

Ages Eligible for Study

18 Years to 65 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

Washington University School of Medicine,

Study Record Dates

2026-07-01