Dr. Bethany Cummings
There is a pressing need for new therapeutic strategies for addressing the epidemic of obesity and its co-morbidities. Bariatric surgery, such as Roux-en-Y Gastric Bypass (RYGB) and vertical sleeve gastrectomy surgery (VSG), is currently the most effective treatment for obesity and often results in remission or decreased risk of co-morbidities, such as type 2 diabetes, hypertension and cancer. However, the mechanisms by which this occurs are undefined. Improvements glucose regulation and blood pressure often occur before significant body weight loss, suggesting that these improvements happen independently of body weight loss. Identification of the mechanisms underlying these surgically-induced benefits may allow for the development of novel therapies for managing obesity and its co-morbidities. Thus, the overall theme of our research program is developing, standardizing and studying animal models of bariatric surgery with the goal of identifying the mechanisms by which bariatric surgery causes these metabolic improvements. Several post-operative changes have been suggested to contribute to the benefits of bariatric surgery, including increases in circulating glucagon like peptide-1 (GLP-1) and bile acid concentrations.
GLP-1 is a hormone secreted by gastrointestinal enteroendocrine cells in response to nutrient ingestion. GLP-1 contributes to postprandial glucose clearance by acting as an incretin hormone to potentiate glucose-stimulated insulin secretion. GLP-1 signaling promotes several other metabolic benefits, including decreased energy intake, improved insulin sensitivity and improved lipid metabolism. Therefore, GLP-1 has become an important therapeutic target in the clinical management of obesity and type 2 diabetes. Nutrient-stimulated GLP-1 secretion is remarkably enhanced after several types of bariatric surgery, including RYGB and VSG. Given the anti-diabetic actions of GLP-1 signaling, elevations in circulating GLP-1 concentrations may contribute to post-operative improvements in glucose regulation.
Circulating bile acid concentrations are elevated after several types of bariatric surgery, including RYGB and VSG. Bile acids are amphipathic steroid molecules with detergent properties that aid in the digestion of dietary cholesterol and lipid. Bile acids also contribute to glucose homeostasis by signaling through several receptors, including TGR5. TGR5 is a transmembrane G protein coupled receptor that acts to maintain glucose homeostasis and decreases inflammatory cytokine secretion. The contributions of post-operative changes in GLP-1 and bile acids are being assessed through genetic and pharmaceutical approaches in rodent models of VSG, RYGB and ileal interposition.
Graduate Field Memberships
Comparative Biomedical Sciences
Molecular and Integrative Physiology
Graduate Field of Nutrition
- Garibay D, McGavigan AK, Lee SA, Ficorilli JV, Cox AL, Michael MD, Sloop KW, Cummings BP. Beta-cell glucagon like peptide-1 receptor contributes to improved glucose tolerance after vertical sleeve gastrectomy. Endocrinology, 2016; 157(9): 3405-9.
- McGavigan AK, Garibay D, Henseler Z, Chen J, Bettaieb A, Haj FG, Ley RE, Chouinard ML, Cummings BP. TGR5 contributes to glucoregulatory improvements after sleeve gastrectomy in mice. Gut. 2015; 0:1-9.
- Mann S, Leal Yepes FA, Duplessis M, Wakshlag JJ, Overton TR, Cummings BP, Nydam DV. Dry period plane of energy: effects on glucose tolerance in transition dairy cows. Journal of Dairy Science. 2015; 99(1):701-17.
- Frank L, Mann S, Levine CB, Cummings BP, Wakshlag JJ. Increasing body condition score is positively associated interleukin-6 and monocyte chemoattractant protein-1 in Labrador retrievers. Vet Immunol Immunopathol. 2015; 167(3-4):104-9.
- Streeter RM, Struble AM, Nydam DV, Bauer JE, Castellano M, Todhunter RJ, Cummings BP, Wakshlag JJ. The associations between serum adiponectin, leptin, c-reactive protein and insulin and serum long-chain omega three fatty acids in Labrador retrievers. Veterinary Medicine: Research and Reports. 2015; 6:103-110.
- Bu P, Wang L, Chen K, Rakhilin N, Sun J, Closa A, Tung K, King S, Varanko AK, Yitian Xu Y, Chen JH, Zessin AS, Shealy J, Cummings BP, Hsu D, Lipkin SM, Moreno V, Gümüş ZH, Shen X. miR-1269 Promotes Metastasis and Forms a Positive Feedback Loop with TGF-β. Nat Communications. 2015; 6:6879.
- Alley JB, Laferrere B, Cummings BP. A road to remission: Multiple perspectives – Bariatric surgery and its effect on metabolic disease. Endocrine News: Tri-Point Series. Endocrine News: Tri-Point Series: 26-30, April 2015.
- Cummings BP. Duodenal exclusion devices: promising tools in treating obesity and type 2 diabetes. Gut. 2014; 63(8):1201-2.
- Cummings BP. Leptin therapy in type 2 diabetes. Diabetes, Obes Metab. 2013; 15(7): 607-12.
- Cummings BP, Bettaieb A, Graham JL, Stanhope KL, Giulivi C, Hansen F, Jelsing J, Vrang N, Kowala M, Chouinard ML, Haj FG, Havel PJ. Bile acid mediated decreases of endoplasmic reticulum stress: a novel contributor to the metabolic benefits of ileal interposition surgery. Dis Models Mech. 2013; 6(2): 443-56.
- Cummings BP, Bettaieb A, Graham GL, Stanhope KL, Kowala M, Chouinard ML, Haj FG, Havel PJ. Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD-T2DM rats. Endocrinology 2012; 153(8):3620-32.
- Cummings BP, Bettaieb A, Graham JL, Stanhope KL, Dill R, Morton GJ, Haj FG and Havel PJ. Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats. Proc Natl Acad Sci. 2011; 108(35):14670-5.
- Cummings BP, Strader AD, Stanhope KL, Graham JL, Lee J, Raybould HE, Baskin DG, Havel PJ. Ileal Interposition Surgery Improves Glucose and Lipid Metabolism and Delays Diabetes Onset in the UCD-T2DM Rat. Gastroenterology. 2010; 138(7):2437-U302.
- Cummings BP, Stanhope KL, Graham JL, Baskin DG, Griffen SC, Nilsson C, Sams A, Knudsen LB, Raun K, Havel PJ. Chronic Administration of the Glucagon-Like Peptide-1 (GLP-1) Analog, Liraglutide, Delays the Onset of Diabetes and Lowers Triglycerides in UCD-T2DM Rats. Diabetes. 2010; 59(10): 2653-61.