40 Participants Needed

KATP Channel Loss for Type 2 Diabetes

(BC Trial)

KT
Overseen ByKyle Timmons
Age: 18+
Sex: Any
Trial Phase: Academic
Sponsor: Washington University School of Medicine
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have changed their diabetes medication in the past 3 months or use medications that could affect the study's outcomes. It's best to discuss your specific medications with the research team.

Is the KATP channel treatment generally safe for humans?

Research on diazoxide, a drug that affects KATP channels, shows it can increase insulin secretion without harmful effects on beta cell function, suggesting it may be safe for long-term use. However, diazoxide can also cause arrhythmias (irregular heartbeats) in people with type 2 diabetes, indicating potential safety concerns.12345

How does the KATP channel loss treatment for type 2 diabetes differ from other treatments?

The KATP channel loss treatment is unique because it targets the ATP-sensitive potassium channels in pancreatic beta cells, which are crucial for insulin secretion. Unlike other treatments that may focus on increasing insulin sensitivity or directly stimulating insulin release, this approach addresses the impaired glucose response by modifying the function of these specific channels, potentially offering a novel way to manage insulin secretion in type 2 diabetes.36789

What data supports the effectiveness of the drug Glipizide for Type 2 Diabetes?

Research shows that ATP-sensitive K+ (KATP) channels play a crucial role in insulin secretion, and sulfonylureas like Glipizide work by affecting these channels to help control blood sugar levels in people with Type 2 Diabetes.136810

Are You a Good Fit for This Trial?

This trial is for adults with type 2 diabetes, who may also have high blood pressure and obesity. Participants should not be on any medication that affects KATP channels or insulin secretion. Pregnant women and individuals with other significant health issues are excluded.

Inclusion Criteria

I am obese with a BMI between 30 and 50, normal blood sugar levels, and no diabetes.
Lean-normoglycemic group: 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%
I am obese with a BMI between 30 and 50, have type 2 diabetes, and am on medication for it.
See 1 more

Exclusion Criteria

I do not have major organ problems except for obesity and type 2 diabetes.
Unstable weight (>2% change during the last 2 months before entering the study)
Regular use of tobacco products
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of the KATP antagonist glipizide (5mg) to assess insulin secretion

1 day
1 visit (in-person)

Follow-up

Participants are monitored for insulin secretion and KATP channel activity after glipizide ingestion

90 minutes
1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • Glipizide
Trial Overview The study tests the effects of a single dose of glipizide, a drug that inhibits KATP channels in the pancreas, which could affect insulin release and blood sugar control in people with type 2 diabetes compared to those without it.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Obesity with type 2 diabetesExperimental Treatment1 Intervention
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.
Group II: Obesity with normal glucose toleranceExperimental Treatment1 Intervention
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%.
Group III: Obesity with impaired fasting glucoseExperimental Treatment1 Intervention
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.
Group IV: Lean with normal glucose toleranceExperimental Treatment1 Intervention
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%.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials
2,027
Recruited
2,353,000+

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

Collaborator

Trials
2,513
Recruited
4,366,000+

Published Research Related to This Trial

The study highlights the importance of ATP-sensitive K+ (KATP) channels in insulin secretion, showing that their absence leads to a shift in G protein signaling in β cells, which affects how incretins like GLP-1 and GIP function in type 2 diabetes (T2D).
GLP-1 can effectively enhance insulin secretion in KATP channel-deficient models, while GIP cannot, suggesting that targeting GLP-1 signaling may be a more effective strategy for improving insulin response in patients with T2D.
Preferential Gq signaling in diabetes: an electrical switch in incretin action and in diabetes progression?Nichols, CG., York, NW., Remedi, MS.[2021]
Transgenic mice expressing a dominant-negative form of the KATP channel subunit Kir6.2 developed significant metabolic issues, including hypoglycemia with hyperinsulinemia in neonates and hyperglycemia with hypoinsulinemia in adults, indicating the critical role of KATP channels in glucose regulation.
The study revealed that impaired KATP channel function in pancreatic beta cells led to increased apoptosis and altered cellular conditions, suggesting that KATP channels are essential not only for insulin secretion but also for the survival of beta cells.
Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel.Miki, T., Tashiro, F., Iwanaga, T., et al.[2019]
Sulfonylureas play a crucial role in regulating glucose-induced electrical activity in pancreatic beta-cells by interacting with ATP-sensitive K channels (KATP), which are essential for insulin secretion.
Recent advancements in understanding the sulfonylurea receptor and KATP channel may provide insights into their complex regulation and improve our knowledge of beta-cell function in diabetes management.
The beta-cell response to oral hypoglycemic agents.Cook, DL.[2019]

Citations

Preferential Gq signaling in diabetes: an electrical switch in incretin action and in diabetes progression? [2021]
Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel. [2019]
The beta-cell response to oral hypoglycemic agents. [2019]
Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. [2023]
Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehyde and oxidizing agent of ATP-sensitive K+ channels of pancreatic beta cells in NIDDM rats. [2015]
The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus. [2022]
Alterations of insulin secretion following long-term manipulation of ATP-sensitive potassium channels by diazoxide and nateglinide. [2018]
Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. [2019]
KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state. [2022]
Energy depletion and not ROS formation is a crucial step of glucolipotoxicity (GLTx) in pancreatic beta cells. [2019]
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