Role of Neural and Hormonal Regulation Factors on Insulin Secretion After Gastric Bypass Surgery

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls.

RYGB (roux-en-y gastric bypass) has been reported to reverse type 2 diabetes (T2DM) immediately after surgery before any significant weight loss. In addition, a growing number of patients have been recognized with life-threatening hyperinsulinemic hypoglycemia several years following their surgery. While the mechanisms by which RYGB improves glucose metabolism or alters islet cell function in patients after RYGB are not understood, recent studies suggest that increased secretion of GI hormones, primarily glucagon-like peptide 1 (GLP-1), as well as alteration in neural activity may contribute to enhanced insulin secretion in general, and to a greater extent in patients with hypoglycemia. The proposed research is designed to address the role of RYGB on insulin secretion by evaluating the contribution of stimulatory factors (neural and GI hormone) on islet cell function and the islet cell responsiveness to the physiologic stimulatory factors, in RYGB patients with and without hypoglycemia and non-operated controls

Eligibility Criteria:
Inclusion Criteria:

* Hypoglycemic RYGB patients with documented blood glucose level \<50 mg/dl
* Asymptomatic individuals with bariatric surgery
* Healthy non-surgical patients with no personal history of diabetes
* Subjects must physically be able to come to our clinical research center at Cedars-Sinai Medical Center

Exclusion Criteria:

* Active heart, lung, liver, gastrointestinal or kidney disease; unable to give informed consent; pregnancy; uncontrolled high blood pressure or high cholesterol; significant anemia (hemoglobin \<11g/dL); prisoners or institutionalized individuals; type 2 diabetes melitis; development of any serious medical or psychiatric illness during recruitment or studies;
* RYGB patients will also be disqualified if they have gastric outlet obstruction or severe diarrhea
* Healthy non-surgical patients with personal history of diabetes

For administration of atropine, the following exclusions also apply:

* History of glaucoma
* Uncontrolled hypertension (any subjects with BP\>140/90 and history of dyslipidemia
* Taking any medication that might interact with atropine and cannot be stopped will be excluded from the study)
* Myasthenia gravis
* Brain pathology
* Enlarged prostate in men