scholarly journals Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jonathan G. Sham ◽  
Vlad V. Simianu ◽  
Andrew S. Wright ◽  
Skye D. Stewart ◽  
Mouhamad Alloosh ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Glucose Homeostasis ◽  
Large Animal ◽  
Miniature Swine ◽  
Intravenous Glucose ◽  
Regular Diet ◽  
Large Animal Models ◽  
Obesogenic Diet ◽  
Intravenous Glucose Tolerance Tests

Background. Roux-en-Y gastric bypass (RYGB) is the most common bariatric operation; however, the mechanism underlying the profound weight-independent effects on glucose homeostasis remains unclear. Large animal models of naturally occurring insulin resistance (IR), which have been lacking, would provide opportunities to elucidate such mechanisms. Ossabaw miniature swine naturally exhibit many features that may be useful in evaluating the anti diabetic effects of bariatric surgery.Methods. Glucose homeostasis was studied in 53 Ossabaw swine. Thirty-two received an obesogenic diet and were randomized to RYGB, gastrojejunostomy (GJ), gastrojejunostomy with duodenal exclusion (GJD), or Sham operations. Intravenous glucose tolerance tests and standardized meal tolerance tests were performed prior to, 1, 2, and 8 weeks after surgery and at a single time-point for regular diet control pigs.Results. High-calorie-fed Ossabaws weighed more and had greater IR than regular diet controls, though only 70% developed IR. All operations caused weight-loss-independent improvement in IR, though only in pigs with high baseline IR. Only RYGB induced weight loss and decreased IR in the majority of pigs, as well as increasingAUCinsulin/AUCglucose.Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increasedAUCinsulin/AUCglucose, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis.

scholarly journals SUN-637 The Impact of Hyperandrogenemia and Western-Style Diet on Post-Pregnancy Metabolism in Nonhuman Primates

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Diana Lynn Takahashi ◽  
Emily Mishler ◽  
Ov Daniel Slayden ◽  
Jon D Hennebold ◽  
Charles T Roberts ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Fat ◽  
Glucose Homeostasis ◽  
Polycystic Ovary ◽  
Mean Value ◽  
Fat Percentage ◽  
Primate Model ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance Tests ◽  
The Impact

Abstract Polycystic ovary syndrome (PCOS) often is associated with hyperandrogenemia and an increased incidence of obesity and type 2 diabetes. To understand the separate and combined effects of androgens and obesity on reproductive and metabolic parameters, our group established a nonhuman primate model consisting of animals receiving either testosterone (T, mean value of 1.4 ng/mL), an obesogenic western-style diet (WSD, 36% of calories from fat compared to 16% in normal monkey chow), or a combination of T+WSD. T+WSD increased insulin resistance compared to WSD alone after three years of treatment and reduced fertility. Those T+WSD animals that became pregnant had a mild worsening of glucose homeostasis during pregnancy. The current study sought to determine how T+WSD affected post-pregnancy metabolic health and whether T+WSD led to the worsening of insulin resistance after pregnancy. Intravenous glucose tolerance tests (ivGTT) were performed 1) before pregnancy, 2) approximately 3-4 months after C-section, which occurred between gestational day 130-135 (3rd trimester), and 3) one year post C-section. All animal groups tended to show increases in weight, BMI, and body fat percentage after pregnancy. Both WSD groups (WSD and T+WSD) had higher overall weights, BMI, and body fat percentages. Measures of insulin sensitivity such as fasting insulin, glucose, and insulin area under the curves during an ivGTT and homeostatic model of insulin resistance (HOMA-IR) all increased over time, but there were no differences between groups. The lack of treatment effect on measures of insulin resistance may be due to the fact that animals that did not become pregnant had significantly higher indices of insulin resistance. Experimental animals underwent a second round of fertility trials thereby allowing for a comparison of glucose homeostasis for those animals that became pregnant in both the 1st and 2nd trial. The WSD group demonstrated increased fasting glucose and glucose AUC during an early third trimester ivGTT in the second pregnancy compared to the first. The control, T, and T+WSD groups did not show significant differences in glucose homeostasis between the first and second pregnancy. These findings indicate that WSD consumption may increase the risk of worsened glucose homeostasis after pregnancy and during subsequent pregnancies. Testosterone, either in isolation or in combination with WSD, did not appear to have a significant impact on post-pregnancy metabolism or worsen metabolic outcomes in a second pregnancy.

scholarly journals Establishment of transplantable porcine tumor cell lines derived from MHC- inbred miniature swine

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3996-4004 ◽  
Author(s):  
Patricia S. Cho ◽  
Diana P. Lo ◽  
Krzysztof J. Wikiel ◽  
Haley C. Rowland ◽  
Rebecca C. Coburn ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Line ◽  
Blood Analysis ◽  
Large Animal ◽  
Tumor Cell Lines ◽  
Miniature Swine ◽  
Serial Transfer ◽  
Large Animal Models ◽  
Immunocompromised Mice

Abstract The lack of transplantable tumors has limited assessment of graft-versus-tumor effects following hematopoietic cell transplantation in clinically relevant large-animal models. We describe the derivation and characterization of porcine tumor cell lines with initial efforts of tumor transplantation using immunocompromised mice and highly inbred sublines of Massachusetts General Hospital major histocompatibility complex (MHC)–inbred miniature swine. Autopsies were performed routinely on swine that died unexpectedly or had suspicion of malignancy based on clinical symptoms or peripheral blood analysis. Tissue samples were obtained for pathology, phenotyped by flow cytometry, and placed in culture. Based on growth, lines were selected for passage into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and miniature swine. Porcine tumor recipients were preconditioned with total body irradiation from 0 to 500 cGy or with a 30-day course of oral cyclosporine. We identified 19 cases of hematologic tumors. Nine distinct tumor cell lines were established from 8 of these cases, including 3 derived from highly inbred sublines. In vivo tumor growth and serial transfer were observed in immunocompromised mice for one tumor cell line and in miniature swine for 1 of 2 tumor cell lines expanded for this purpose. These results suggest the possibility of developing a transplantable tumor model in this large-animal system.

scholarly journals Role of the Thymus in Transplantation Tolerance in Miniature Swine. I. Requirement of the Thymus for Rapid and Stable Induction of  Tolerance to Class I–mismatched Renal Allografts

1997 ◽  
Vol 186 (4) ◽  
pp. 497-506 ◽  
Author(s):  
Kazuhiko Yamada ◽  
Pierre R. Gianello ◽  
Francesco L. Ierino ◽  
Thomas Lorf ◽  
Akira Shimizu ◽  
...  
Keyword(s):  
T Cell ◽  
Class I ◽  
Striking Difference ◽  
Large Animal ◽  
Miniature Swine ◽  
Renal Allografts ◽  
Large Animal Models ◽  
Induction Of Tolerance

The almost uniform failure in transplant patients of tolerance-inducing regimens that have been found to be effective in rodents, has made it necessary to examine large animal models before testing of new approaches clinically. Miniature swine have been shown to share many relevant immunologic parameters with humans, and because of their reproducible genetics, have proved extremely useful in providing such a large animal model. We have previously shown that indefinite systemic tolerance to renal allografts in miniature swine is induced in 100% of cases across a two-haplotype class I plus minor histocompatibility antigen disparity by a 12-d course of Cyclosporine A (CyA), in contrast to irreversible rejection observed uniformly without CyA treatment. In the present study, we have examined the role of the thymus during the induction of tolerance by performing a complete thymectomy 21 d before renal transplantation. This analysis demonstrated a striking difference between thymectomized and nonthymectomized animals. Thymectomized swine developed acute cellular rejection characterized by a T cell (CD25+) infiltrate, tubulitis, endothelialitis and glomerulitis, and anti–donor CTL reactivity in vitro. Nonthymectomized and sham thymectomized animals had a mild T cell infiltrate with few CD25+ cells and no anti–donor CTL response in vitro. These results indicate that the thymus is required for rapid and stable induction of tolerance.

scholarly journals Non-Invasive Characterization of the Pancreas During Bariatric Surgery via Circulating Pancreatic Specific Cell-free Messenger RNA

2021 ◽  
Vol 12 ◽  
Author(s):  
Kong Kiat Whye ◽  
E ShyongTai ◽  
Asim Shabbir ◽  
Chin Meng Khoo ◽  
Winston Koh
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Glucose Homeostasis ◽  
Messenger Rna ◽  
Specific Cell ◽  
Haemoglobin A1c ◽  
Multiple Time ◽  
Short Term ◽  
Non Invasive ◽  
Post Surgery

Bariatric surgery results in sustained weight loss and improvement in glucose homeostasis. However, the lack of accessible non-invasive tools to examine molecular alterations occurring in the pancreas limits our understanding of the causes and recovery of glucose homeostasis. Here, we describe the use of a circulating cell free mRNA (cfmRNA) based multiplex qPCR assay to selectively amplify and quantify circulating pancreatic specific transcripts levels within plasma. We applied this assay to a cohort of 58 plasma samples consisting of 10 patients that tracks multiple time points including pre and post-bariatric surgery. In our targeted multiplex screen of 14 selected pancreatic specific circulating transcripts, we identified 13 pancreatic specific transcripts that can be amplified from plasma. Furthermore, when quantifying the amplicons obtained in the short-term post-surgery (2 weeks–1 month) and long-term (3–12 months), we observed a consistent reduction of circulating GCG transcripts during short term post-surgery. Across the cohort, GCG cfmRNA levels correlated significantly with common metrics of improvement following bariatric surgery such as: haemoglobin A1c levels (R: −0.41, p-value: 0.0039) and percentage of excess weight loss (R: 0.29, p-value: 0.046).

scholarly journals Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 762
Author(s):  
Dimitris Papamargaritis ◽  
Carel W. le Roux
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Glucose Homeostasis ◽  
Hormone Secretion ◽  
Eating Behaviour ◽  
Early Period ◽  
Specific Inhibitor ◽  
Gut Hormones ◽  
Current Evidence ◽  
Gut Hormone

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy—the two most commonly performed bariatric procedures—and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9–39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.

Abstract #240 Weight Loss Trajectory Following Randomization to Bariatric Surgery on Long-Term Diabetes Outcomes

2018 ◽  
Vol 24 ◽  
pp. 49
Author(s):  
Keren Zhou ◽  
Kathy Wolski ◽  
Ali Aminian ◽  
Steven Malin ◽  
Philip Schauer ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Diabetes Outcomes ◽  
Trajectory Following

Long-Term Weight Loss and Psychological Functioning in Bariatric Surgery Patients

2012 ◽  
Author(s):  
Leslie M. Schuh ◽  
David B. Creel ◽  
Joseph Stote ◽  
Katharine Hudson ◽  
Karen K. Saules ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Psychological Functioning

Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice

2018 ◽  
Vol 239 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Lewin Small ◽  
Henry Gong ◽  
Christian Yassmin ◽  
Gregory J Cooney ◽  
Amanda E Brandon
Keyword(s):  
Glucose Metabolism ◽  
Ambient Temperature ◽  
Fat Mass ◽  
Glucose Homeostasis ◽  
Dietary Intervention ◽  
Whole Body ◽  
Housing Temperature ◽  
Brown Adipose ◽  
Normal Chow ◽  
Obesogenic Diet

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.

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