The Effects of Bethanechol on Glucose Homeostasis

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:

* \<18years of age or \>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.