Metabolic Syndrome and Diabetes by Marina Kurian Bruce M. Wolfe & Sayeed Ikramuddin

Author:Marina Kurian, Bruce M. Wolfe & Sayeed Ikramuddin
Language: eng
Format: epub
Publisher: Springer New York, New York, NY

Mallipedhi et al. [87]

VSG/BPD

IGT/T2DM

OGTT

↑

↓

Plourde et al. [88]

BPD

T2DM/NGT

Meal

↑

↓

Kim et al. [64]

RYGBP

Lean T2DM

OGTT

↑

↓

Fig. 9.1Accelerate gastric pouch emptying after RYGBP. (a) Acetaminophen levels during a 600 kcal liquid meal given before or 1 year after RYGBP surgery; (b) Strong relationship between gastric pouch emptying and GLP-1 release during a 600 kcal meal

9.6 Lessons from Rodent Models

Although data in humans and pigs support a role for GLP-1 in controlling glucose after RYGBP, experiments with knock out (KO) animal models challenge the role of GLP-1 in the control of body weight and glucose after RYGBP or VSG. Berthoud et al. [89] showed that chronic brain infusion of exendin-9-39 into the lateral cerebral ventricle similarly increased food intake and body weight in both RYGBP and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weight-lowering effects of RYGBP. In a separate experiment, the same authors showed that obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice after a RYGBP-like procedure [89]. GLP-1 levels are also enhanced after VSG in humans [90] and rodents [91], and are thought to be a mediator of diabetes remission after this surgery [92]. However, VSG-operated GLP-1 receptor-deficient mice respond similarly to wild-type controls in terms of body weight loss, improved glucose tolerance, food intake reduction, and altered food selection [93]. These data demonstrate that GLP-1 receptor activity is not necessary for the metabolic improvements induced by VSG or RYGBP surgery in these animal models. The relevance of these KO experiments to clinical observations is unclear.

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