In autoimmune type 1 diabetes mellitus, proinflammatory cytokine-mediated apoptosis of β-cells has been considered to be the first event directly responsible for β-cell mass reduction. In the Bio-Breeding (BB) rat, an in vivo model used in the study of autoimmune diabetes, β-cell apoptosis is observed from 9 wk of age and takes place after an insulitis period that begins at an earlier age. Previous studies by our group have shown an antiproliferative effect of proinflammatory cytokines on cultured β-cells in Wistar rats, an effect that was partially reversed by Exendin-4, an analogue of glucagon-like peptide-1. In the current study, the changes in β-cell apoptosis and proliferation during insulitis stage were also determined in pancreatic tissue sections in normal and thymectomized BB rats, as well as in Wistar rats of 5, 7, 9, and 11 wk of age. Although stable β-cell proliferation in Wistar and thymectomized BB rats was observed along the course of the study, a decrease in β-cell proliferation and β-cell mass from the age of 5 wk, and prior to the commencement of apoptosis, was noted in BB rats. Exendin-4, in combination with anti-interferon-γ antibody, induced a near-total recovery of β-cell proliferation during the initial stages of insulitis. This highlights the importance of early intervention and, as well, the possibilities of new therapeutic approaches in preventing autoimmune diabetes by acting, initially, in the insulitis stage and, subsequently, on β-cell regeneration and on β-cell apoptosis.

Aims: Roux-en-Y gastric bypass (RYGB) is one of the most effective surgical therapies for the rapid resolution of type 2 diabetes. However, the mechanisms underlying the entero-hormonal response after surgery and the role of peptide tyrosine tyrosine (PYY) in the restoration of normoglycemia are still not clear. Methods: We reproduced the RYGB technique in Wistar and Goto–Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test. Results: Using the diabetic Goto–Kakizaki (GK) rat model, we demonstrated that PYY plasma levels showed a remarkable peak approximately 30 min earlier than GLP-1 or GIP after mixed-meal administration in RYGB-operated rats with PYY. The GLP-1 and GIP areas under the curve (AUCs) increased after RYGB in GK rats. Additionally, the findings suggested that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Finally, the number of GLP-1-positive cells appeared to increase in the three segments of the small intestine in GK-RYGB-operated rats beyond the early presence of nutrient stimulation in the ileum. Nevertheless, PYY-positive cell numbers appeared to increase only in the ileum. Conclusion: At least in rats, these data demonstrate an earlier essential role for PYY in gut hormone regulation after RYGB. We understand that PYY contributes to GLP-1 and GIP release and there must be the existence of enteroendocrine communication routes between the distal and proximal small intestine.

Roux-en-Y gastric bypass (RYGB) is the gold standard method for bariatric surgery and leads to substantial improvements in Type 2 Diabetes mellitus. However, many patients experience relapses in diabetes five years after undergoing this aggressive surgical procedure. We focus on beta-cell population changes and absorptive intestinal consequences after RYGB in a healthy nonobese animal model after a long survival period. For our purpose, we use three groups of Wistar rats: RYGB-operated, surgical control (Sham) and fasting control. We measure alpha-, beta-cell mass; transcription (Arx, and Pdx-1) and proliferation (Ki67) factors; glucose tolerance and insulin release after oral glucose tests; histological adaptive changes in the jejunum; and intestinal glucose transporters. Our results showed an early increase in insulin secretion after surgery, that decrease at the end of the study. The beta-cell mass reduces twenty-four weeks after RYGB, which coincides with decrease of Pdx-1 transcription promoter factor. These was coincident with an increase in alpha-mass and a high expression of Arx in RYGB group. The analysis of all data showed beta-cell mass transdifferentiation into alpha-cell mass in RYGB rats. Due to long-term exhaustion of the beta-cell population by hyperinsulinism derived from digestive tract adaptation to surgery.

Bariatric surgery is an effective treatment for achieving significant weight loss and improving metabolic comorbidities such as type 2 diabetes mellitus (T2DM). The aim of our study was to investigate clinical factors related to T2DM remission in obese patients who had undergone bariatric surgery. Methods: A cohort of patients with T2DM and a minimum of class II obesity undergoing bariatric surgery had their clinical and anthropometric variables assessed. The statistical evaluation included multivariate analyses of clinical factors predicting a T2DM remission two years post-surgery. Results: 83 patients were included (mean age 44.13 ± 10.38 years). Two years post-surgery, the percentage of excess weight lost was 63.43 ± 18.59%, and T2DM was resolved in 79.5% of the patients. T2DM remission was directly related to a high body mass index (BMI) (OR: 1.886; p = 0.022) and the absence of macro-vascular complications (OR: 34.667; p = 0.002), while it was inversely associated with T2DM with a duration longer than 5 years (OR: 0.022; p = 0.040) and baseline insulin treatment (OR: 0.001; p = 0.009). 15.6% of the patients presented early complications and 20.5% developed late complications. Conclusion: In our study sample, bariatric surgery proved to be an effective and safe technique for sustained medium-term weight loss and the resolution of T2DM. A higher baseline BMI, a shorter T2DM duration, non-insulin treatment, and the absence of macro-vascular complications are factors predictive of T2DM remission.