the effects of bethanechol on glucose homeostasis

Conditions: Type 2 Diabetes Mellitus

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: * ages 18-65. no minors will be studied. * individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions). * healthy volunteers with no clinical evidence of t2dm (see below). * otherwise healthy volunteers that have impaired glucose tolerance (see below). * otherwise healthy volunteers with diet controlled t2dm (see below). * otherwise healthy volunteers with t2dm that take oral agents only and if the subject's pre-existing oral anti-diabetic agents can be safely discontinued for 48 hours prior to oral glucose tolerance test. * otherwise healthy volunteers with t2dm who do not use insulin for blood glucose control. * persons with hba1c ≤ 9%. * women of childbearing potential must be currently taking/using a method of birth control that is acceptable to the investigators. a pregnancy test will be done at the beginning of each visit. any woman with a positive pregnancy test will be removed from the study. exclusion criteria: * \ 65 years of age * lacks cognitive ability to sign the consent \&/or follow the study directions for themselves * women unwilling to comply with using an acceptable method of contraception during the course of the study, or who are currently breast-feeding. * any subject whose screening hba1c is \>9.0% * type 2 diabetes requiring the use of supplemental insulin @ home * volunteers with a history of acute pancreatitis * volunteer with a history of chronic pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia (triglycerides \>400mg/ml) hypercalcemia (blood calcium level \>11.md/dl) and/or the presence of gallstones. * volunteers with a history of gastrointestinal disorders, particularly related to gastric motility/emptying such as gastric bypass, documented gastro-paresis in diabetic volunteers. * volunteers with a history of cancer. exception: skin cancer. * diabetics that have the potential to have a low blood sugar without them being aware that their blood sugar is low (hypoglycemia unawareness). * known heart, kidney. liver or pancreatic disease requiring medications. * unwillingness to allow blood glucose level adjustment (if needed) with iv insulin. * subjects with hyperthyroidism, coronary artery disease, peptic ulcer, asthma, chronic bronchitis, or copd.

Keywords: diabetes blood sugar xenin-25 gip muscarinic