The effect of distal-ileal exclusion after Roux-en-Y gastric bypass on glucose tolerance and GLP-1 response in type-2 diabetes Sprague-Dawley rat model

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.

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Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

Endocrine Regulations ◽

10.2478/enr-2018-0008 ◽

2018 ◽

Vol 52 (2) ◽

pp. 69-75 ◽

Cited By ~ 2

Author(s):

Titin Andri Wihastuti ◽

Teuku Heriansyah ◽

Hanifa Hanifa ◽

Sri Andarini ◽

Zuhrotus Sholichah ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Rat Model ◽

Foam Cells ◽

Male Rats ◽

Sprague Dawley ◽

Early Stages ◽

Sprague Dawley Rat

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.

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Distal gastric mucosa ablation induces significant weight loss and improved glycemic control in type 2 diabetes Sprague–Dawley rat model

Surgical Endoscopy ◽

10.1007/s00464-019-07200-3 ◽

2019 ◽

Vol 34 (10) ◽

pp. 4336-4346

Author(s):

Ponnie Robertlee Dolo ◽

Ke Huang ◽

Jason Widjaja ◽

Chao Li ◽

Xiaocheng Zhu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Glycemic Control ◽

Gastric Mucosa ◽

Rat Model ◽

Significant Weight Loss ◽

Sprague Dawley ◽

Sprague Dawley Rat

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Faculty Opinions recommendation of Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717982095.793471985 ◽

2013 ◽

Author(s):

Gina LC Yosten ◽

Molly Elrick

Keyword(s):

Type 2 Diabetes ◽

Gastric Bypass ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Long Term Effects ◽

Normal Glucose

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Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes

Journal of Endocrinology ◽

10.1530/joe-14-0701 ◽

2015 ◽

Vol 228 (1) ◽

pp. 13-23 ◽

Cited By ~ 11

Author(s):

Xinrong Zhou ◽

Bangguo Qian ◽

Ning Ji ◽

Conghui Lui ◽

Zhiyuan Liu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Bypass ◽

Rat Model ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Cell Mass ◽

Cell Area ◽

Obese Patients ◽

Β Cell

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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Dual Mechanism for Type-2 Diabetes Resolution after Roux-en-Y Gastric Bypass

The American Surgeon ◽

10.1177/000313480907500608 ◽

2009 ◽

Vol 75 (6) ◽

pp. 498-503 ◽

Cited By ~ 10

Author(s):

Edward Lin ◽

S. Scott Davis ◽

Jahnavi Srinivasan ◽

John F. Sweeney ◽

Thomas R. Ziegler ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Gastric Bypass ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Peripheral Insulin Resistance

Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose-insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.

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