Xenin-25 and glucose-dependent insulinotropic polypeptide (GIP) are hormones produced in the intestine that are released into the blood immediately after ingestion of a meal. Together, these 2 hormones increase insulin release and reduce blood glucose levels. Xenin-25 works by increasing acetylcholine release in pancreatic islets. This study will determine if a Bethanechol, a drug that is similar to acetylcholine, also increases insulin release and reduces blood glucose levels after ingestion of a mixed meal.
Full Title of Study: “The Effects of Bethanechol, a Muscarinic Agonist, on Plasma Insulin, Glucagon, and Glucose Levels in Humans With and Without Type 2 Diabetes Mellitus”
- Study Type: Interventional
- Study Design
- Allocation: Non-Randomized
- Intervention Model: Crossover Assignment
- Primary Purpose: Basic Science
- Masking: Single (Participant)
- Study Primary Completion Date: July 7, 2014
Each eligible participant will be administered an oral glucose tolerance test (OGTT) so he/she can be assigned to the group with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) which is between normal and diabetic, or type 2 diabetes mellitus (T2DM). Each study subject will then be administered a meal tolerance test (MTT) on 4 separate occasions. For the MTT, a liquid meal (Boost Plus) will be ingested following an overnight fast. A placebo or Bethanechol (25 mg, 50 mg, or 100 mg) will taken by mouth 1 hour before ingestion of the meal. Blood samples will be collected before and during the MTT for the measurement of glucose, insulin, C-peptide, and glucagon levels.
- Drug: Placebo
- A placebo will be taken by mouth 1 hour before ingestion of a mixed meal.
- Drug: Bethanechol (25 mg)
- 25 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
- Drug: Bethanechol (50 mg)
- 50 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
- Drug: Bethanechol (100 mg)
- 100 mg of Bethanechol will be taken by mouth 1 hour before ingestion of a mixed meal
Arms, Groups and Cohorts
- Experimental: Normal Glucose Tolerance
- Healthy individuals exhibiting plasma glucose levels less than 140mg/dl two hours after ingestion of 75-g of glucose.
- Experimental: Impaired Glucose Tolerance
- Healthy individuals exhibiting plasma glucose levels between 140 and 199 mg/dl two hours after ingestion of 75-g of glucose.
- Experimental: Type 2 Diabetes Mellitus
- Healthy individuals exhibiting plasma glucose levels greater than 150 mg/dL under fasting conditions OR greater than 199 mg/dl two hours after ingestion of 75-g of glucose.
Clinical Trial Outcome Measures
- The effects of Bethanechol on insulin secretion rates
- Time Frame: 3 years
- Insulin secretion rates (pmoles/min) will be calculated by deconvolution of plasma C-peptide levels. The investigators will then determine if post-prandial insulin secretion rates are greater following administration of Bethanechol compared to placebo.
Participating in This Clinical Trial
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 65 Years
Are Healthy Volunteers Accepted: Accepts Healthy Volunteers
- Lead Sponsor
- Washington University School of Medicine
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Provider of Information About this Clinical Study
- Overall Official(s)
- Burton M Wice, PhD, Principal Investigator, Washington University School of Medicine
- Dominic Reeds, MD, Principal Investigator, Washington University School of Medicine
Citations Reporting on Results
Chowdhury S, Wang S, Dunai J, Kilpatrick R, Oestricker LZ, Wallendorf MJ, Patterson BW, Reeds DN, Wice BM. Hormonal Responses to Cholinergic Input Are Different in Humans with and without Type 2 Diabetes Mellitus. PLoS One. 2016 Jun 15;11(6):e0156852. doi: 10.1371/journal.pone.0156852. eCollection 2016.
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