Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat.
OBJECTIVE
Obesity-related diabetes is caused by insulin resistance and beta-cell dysfunction. The current study examines changes in food intake, weight loss, body fat depots, oxygen consumption, insulin sensitivity, and incretin levels as potential mechanisms for improved glucose tolerance after Roux-en-Y gastric bypass (RYGB).


METHODS
Three groups of genetically obese Zucker rats were studied: RYGB, sham surgery pair-fed (PF), and sham surgery ad libitum (AL) fed rats. Changes in body weight, visceral and subcutaneous fat depots, oral glucose tolerance, insulin sensitivity, and the plasma concentrations of insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide, and peptide YY (PYY) were measured.


RESULTS
Body weight and subcutaneous fat were decreased after RYGB, compared with the PF and AL groups. The reduction in visceral fat after RYGB appeared largely because of food restriction. Glucose tolerance and insulin sensitivity were significantly improved in only the RYGB group (P < 0.05 vs. AL, PF). Euglycemic, hyperinsulinemic clamp studies indicated RYGB improved the ability of insulin to stimulate peripheral (eg, skeletal muscle) glucose uptake. Fasting total GLP-1, glucose-dependent insulinotropic peptide, and PYY levels were similar between the groups, whereas postprandial plasma levels of intact GLP-1 (7-36) amide, total GLP-1, and PYY were increased in the RYGB group compared with PF and AL controls.


CONCLUSIONS
Glucose homeostasis after RYGB is associated with decreased subcutaneous fat, increased postprandial PYY, GLP-1, and insulin, as well as improved insulin sensitivity/action. Changes in food intake and visceral fat do not seem to explain improvements in insulin action after RYGB in the Zucker rat model.
Meirelles
Katia
K
Departments of Surgery, Pennsylvania State University College of Medicine, Hershey, 17033, USA.
Ahmed
Tamer
T
Culnan
Derek M
DM
Lynch
Christopher J
CJ
Lang
Charles H
CH
Cooney
Robert N
RN
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004195:Disease Models, Animal; D015390:Gastric Bypass; D006706:Homeostasis; D008297:Male; D009767:Obesity, Morbid / Q000097:blood / Q000378:metabolism* / Q000601:surgery*; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose