Preserving Duodenal-Jejunal (Foregut) Transit Does Not Impair Glucose Tolerance and Diabetes Remission Following Gastric Bypass in Type 2 Diabetes Sprague-Dawley Rat Model

2017 ◽  
Vol 28 (5) ◽  
pp. 1313-1320 ◽  
Author(s):  
Ponnie R. Dolo ◽  
Libin Yao ◽  
Chao Li ◽  
Xiaocheng Zhu ◽  
Linsen Shi ◽  
...  
2019 ◽  
Vol 29 (6) ◽  
pp. 1889-1900 ◽  
Author(s):  
Ponnie Robertlee Dolo ◽  
Yong Shao ◽  
Chao Li ◽  
Xiaocheng Zhu ◽  
Libin Yao ◽  
...  

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1588-1597 ◽  
Author(s):  
Andrew C. Shin ◽  
Huiyuan Zheng ◽  
R. Leigh Townsend ◽  
David L. Sigalet ◽  
Hans-Rudolf Berthoud

Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for morbid obesity and remission of associated type 2 diabetes, but the mechanisms involved are poorly understood. The aim of the present study was to develop and validate a rat model for RYGB surgery that allows repeated measurement of meal-induced changes in gut and pancreatic hormones via chronic venous catheters. Male Sprague Dawley rats made obese on a palatable high-fat diet were subjected to RYGB or sham surgery and compared with chow-fed, lean controls. Hormonal responses to a mixed-liquid test meal were examined by frequent blood sampling through chronically implanted jugular catheters in freely behaving rats, 3–4 months after surgery, when RYGB rats had significantly reduced body weight and fat mass compared with sham-operated rats. Hyperleptinemia, basal hyperinsulinemia, and hyperglycemia as well as postprandial glucose intolerance seen in sham-operated, obese rats were completely reversed by RYGB and no longer different from lean controls. Postprandial increases in glucagon-like peptide-1, peptide YY, and amylin as well as suppression of ghrelin levels were all significantly augmented in RYGB rats compared with both sham-operated obese and lean control rats. Thus, our rat model replicates most of the salient hormonal and glycemic changes reported in obese patients after RYGB, with the addition of amylin to the list of potential candidate hormones involved in hypophagia, weight loss, and remission of diabetes. The model will be useful for elucidating the specific peripheral and central mechanisms involved in the suppression of appetite, loss of body weight, and remission of type 2 diabetes.


2018 ◽  
Vol 52 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Titin Andri Wihastuti ◽  
Teuku Heriansyah ◽  
Hanifa Hanifa ◽  
Sri Andarini ◽  
Zuhrotus Sholichah ◽  
...  

AbstractObjective. Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.Methods. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.Results. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.Conclusion. Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.


2019 ◽  
Vol 34 (10) ◽  
pp. 4336-4346
Author(s):  
Ponnie Robertlee Dolo ◽  
Ke Huang ◽  
Jason Widjaja ◽  
Chao Li ◽  
Xiaocheng Zhu ◽  
...  

2021 ◽  
Vol 9 (1) ◽  
pp. e002033
Author(s):  
Erik Stenberg ◽  
Torsten Olbers ◽  
Yang Cao ◽  
Magnus Sundbom ◽  
Anders Jans ◽  
...  

IntroductionBariatric and metabolic surgery is an effective treatment option for type 2 diabetes (T2D). Increased knowledge regarding factors associated with diabetes remission is essential in individual decision making and could guide postoperative care. Therefore, we aimed to explore factors known to affect the chance of achieving diabetes remission after bariatric and metabolic surgery and to further investigate the impact of socioeconomic factors.Research design and methodsIn this nationwide study, we assessed all patients with T2D who underwent Roux-en-Y gastric bypass (RYGB) surgery between 2007 and 2015 in the Scandinavian Obesity Surgery Registry. Remission was defined as absence of antidiabetic medication for T2D 2 years after surgery. Multivariable logistic regression was used to evaluate factors associated with diabetes remission, with missing data handled by multiple imputations.ResultsA total of 8057 patients were included. Mean age±SD was 47.4±10.1 years, mean body mass index 42.2±5.7 kg/m2, mean hemoglobin A1c 59.0±17.33, and 61.7% (n=4970) were women. Two years after surgery, 6211 (77.1%) patients achieved T2D remission. Preoperative insulin treatment (OR 0.26, 95% CI 0.22 to 0.30), first-generation immigrant (OR 0.66, 95% CI 0.57 to 0.77), duration of T2D (OR 0.89, 95% CI 0.88 to 0.90), dyslipidemia (OR 0.71, 95% CI 0.62 to 0.81), age (OR 0.97, 95% CI 0.96 to 0.97), and high glycosylated hemoglobin A1c (HbA1c) (OR 0.99, 95% CI 0.98 to 0.99) were all associated with lower T2D remission rate. In contrast, residence in a medium-sized (OR 1.39, 95% CI 1.20 to 1.61) or small (OR 1.46, 95% CI 1.25 to 1.71) town and percentage of total weight loss (OR 1.04, 95% CI 1.03 to 1.04) were associated with higher remission rates.ConclusionAmong patients with T2D undergoing RYGB surgery, increasing age, HbA1c, and diabetes duration decreased the chance of reaching diabetes remission without cut-offs, while postoperative weight loss demonstrated a positive linear association. In addition, being a first-generation immigrant and living in a large city were socioeconomic factors having a negative association.


2015 ◽  
Vol 228 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Xinrong Zhou ◽  
Bangguo Qian ◽  
Ning Ji ◽  
Conghui Lui ◽  
Zhiyuan Liu ◽  
...  

Gastric bypass surgery produces clear antidiabetic effects in a substantial proportion of morbidly obese patients. In view of the recent trend away from ‘bariatric’ surgery and toward ‘metabolic’ surgery, it is important to elucidate the enhancing effect of bypass surgery on pancreatic β-cell mass, which is related to diabetes remission in non-obese patients. We investigated the effects of gastric bypass surgery on glycemic control and other pancreatic changes in a spontaneous non-obese type 2 diabetes Goto-Kakizaki rat model. Significant improvements in postprandial hyperglycemia and plasma c-peptide level were observed when glucose was administered orally post-surgery. Other important events observed after surgery were enhanced first phase insulin secretion in a in site pancreatic perfusion experiment, pancreatic hyperplasia, improved islet structure (revealed by immunohistochemical analysis), striking increase in β-cell mass, slight increase in ratio of β-cell area to total pancreas area, and increased number of small islets closely related to exocrine ducts. No notable changes were observed in ratio of β-cell to non-β endocrine cell area, β-cell apoptosis, or β-cell proliferation. These findings demonstrate that gastric bypass surgery in this rat model increases endocrine cells and pancreatic hyperplasia, and reflect the important role of the gastrointestinal system in regulation of metabolism.


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