Increased β-Cell Mass in Obese Rats after Gastric Bypass: A Potential Mechanism for Improving Glycemic Control

Abstract

BACKGROUND Over the past few decades, bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become widely considered the most effective treatment for morbid obesity. In most cases, it results in enhanced glucose management in patients with obesity and type 2 diabetes (T2D), which is observed before significant weight loss. However, what accounts for this effect remains controversial. To gain insight into the benefits of RYGB in T2D, we investigated changes in the β-cell mass of obese rats following RYGB. MATERIAL AND METHODS RYGB or a sham operation was performed on obese rats that had been fed a high-fat diet (HFD) for 16 weeks. Then, the HFD was continued for 8 weeks in both groups. Additional normal chow diet (NCD) and obese groups were used as controls. RESULTS In the present study, RYGB induced improved glycemic control and enhanced β-cell function, which was reflected in a better glucose tolerance and a rapidly increased secretion of insulin and C-peptide after glucose administration. Consistently, rats in the RYGB group displayed increased β-cell mass and islet numbers, which were attributed in part to increased glucagon-like peptide 1 levels following RYGB. CONCLUSIONS Our data indicate that RYGB can improve b-cell function via increasing β-cell mass, which plays a key role in improved glycemic control after RYGB.

Figure 1

Systemic metabolic effects of the high-fat diet (HFD) and Roux-en-Y gastric bypass (RYGB). (A) Body weight progression from the start of the HFD (n=6 per group). (B) Body weight progression after RYGB or the sham operation (n=6 per group). (C) Epididymal fat weight 8 weeks after surgery (n=4 per group). (D) Total fat mass measured by dual-energy X-ray absorptiometry 8 weeks after surgery (n=4 per group).

Figure 2

Evaluation of β-Cell function after surgery. (A) Intraperitoneal glucose tolerance test (after 8 h of fasting, 2 g/kg glucose) 6 weeks after surgery (n=4 per group). (B) Fasting and postprandial (30 min after glucose administration) insulin levels 6 weeks after surgery (n=6 per group). (C) Fasting and postprandial (30 min after glucose administration) C-peptide levels 6 weeks after surgery (n=6 per group). (D) The homeostatic model assessment for assessing insulin resistance index (calculated as fasting glucose level (mmol/L) × fasting insulin level (mIU/L)/22.5) 6 weeks after surgery (n=6 per group).

Figure 3

Representative images of pancreatic sections immunohistochemically stained for insulin (dark brown). All slides were counterstained with hematoxylin and imaged at ×5 objective magnification. (A) Pancreatic section from a rat fed the normal chow diet. (B) Pancreatic section from a rat fed the high-fat diet. (C) Pancreatic section from a rat that underwent Roux-en-Y gastric bypass. (D) Pancreatic section from a rat that underwent the sham operation. Scale bars=100 μm.

Figure 4

Pancreatic morphology in the different groups. (A) Ratio of pancreas weight to body weight (%). (B) Relative β-Cell volume (RCV, %). (C) β-Cell mass (mg, quantified by multiplying pancreas weight by RCV). (D) Mean size of individual β-Cell. (E) Number of islets per unit area of total tissue. (F) Mean islet size of rats in the different groups. N=6 per group for all assays.

Figure 5

GLP-1 levels after surgery (after 8 h of fasting, n=6 per group).