Hyperglycemia Induced Hyperexcitability: A Novel Role for KATP in the Progression of Type 2 Diabetes
Washington University School of Medicine
Summary
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.
Description
The worldwide epidemic of obesity has developed alongside, and is causally linked to, the epidemic of insulin resistance and type 2 diabetes mellitus (T2DM). Plasma insulin concentrations are typically elevated in people with insulin resistance attributable to an increase in insulin secretion rate by pancreatic β-cells; however, in people with T2DM, β-cells eventually fail to 'keep up' and there is a crossover from insulin hypersecretion to undersecretion. In the β-cell, KATP channels serve as the link between rising glucose and insulin secretion. Unlike other cells in the body, the uptake of…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Lean-normoglycemic group (n=10): BMI ≥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%. * Obesity-normoglycemic group (n=10): BMI ≥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%. * 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 g…
Interventions
- Drug10 mg glipizide ingestion
A single dose of 10 mg glipizide will be ingested
Location
- Washington University in St. LouisSt Louis, Missouri