Dr. Bethany Cummings
My laboratory studies the etiology and treatment of obesity, insulin resistance and type 2 diabetes. The prevalence of obesity and type 2 diabetes is rapidly expanding, creating a pressing need for the development of novel preventative and therapeutic strategies for obesity and type 2 diabetes. Bariatric surgery, such as Roux-en-Y Gastric Bypass (RYGB) surgery, is currently the most effective treatment for obesity and often results in resolution of type 2 diabetes. However, the mechanisms by which this occurs are undefined. Identification of the major mechanisms underlying surgically-induced improvements of glucose metabolism may allow for the development of novel therapies for managing obesity and treating type 2 diabetes. Therefore, we are developing, standardizing and studying animal models of bariatric surgery with the goal of identifying the mechanisms by which bariatric surgery causes diabetes resolution and prevention. The three potential mechanisms that we are currently focusing on are: post-operative increases of postprandial glucagon-like peptide-1 (GLP-1) secretion, increases of circulating bile acid concentrations and decreases of circulating ghrelin concentrations. The changes of GLP-1, bile acids, and ghrelin have been well described in both rodent and human clinical studies, however the actual contributions of each of these changes to the metabolic improvements following bariatric surgery have not been previously demonstrated or quantified. Therefore, studies in our lab are focused on evaluating the contributions made by each of these post-operative changes to the metabolic benefits of bariatric surgery. We are approaching this question using both pharmaceutical addition and ablation techniques in a type 2 diabetic rat model and genetic knockout mouse models.
Graduate Field Memberships
Comparative Biomedical Sciences
Molecular and Integrative Physiology
- Cummings BP. Duodenal exclusion devices: promising tools in treating obesity and type 2 diabetes. Gut. In press.
- Cummings BP, Graham JL, Stanhope K and Havel PJ. Maternal ileal interpostion surgery confers metabolic improvements to offspring independent of effects on maternal body weight. Obesity Surgery. 2013; 23(12): 2042-9.
- 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.
- Rountree A, Reed BJ, Cummings BP, Jung SR, Stanhope KL, Graham JL, Griffen SC, Hull R, Havel PJ, Sweet IR. Loss of coupling between calcium influx, energy consumption, and insulin secretion associated with development of hyperglycemia in the UCD-T2DM rat model of type 2 diabetes. Diabetologia. 2013; 56(4): 803-13.
- Cummings BP, Bremer AA, Keiffer TJ, D’Alessio D and Havel PJ. Investigation of the mechanisms contributing to the compensatory increase of insulin secretion during dexamethasone-induced insulin resistance in rhesus macaques. J Endocrinol. 2013; 216(2): 207-15.
- Cummings BP. Leptin therapy in type 2 diabetes. Diabetes, Obes Metab. 2012; 15(7): 607-12.
- 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.
- Lee J, Cummings BP, Martin E, Graham JL, Stanhope KL, Sharp JW, Havel PJ, Raybould HE. Glucose-sensing by Gut Endocrine Cells and activation of the Vagal Afferent Pathway is Impaired with diabetes exposure in a Rodent Model of Type 2 Diabetes Mellitus. Am J Physiol Regul Integr Comp Physiol. 2012; 302(6):R657-66.
- 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.
- Cummings BP, Digitale EK, Stanhope KL, Graham JL, Baskin DG, Reed BJ, Sweet IR, Griffen SC, Havel PJ. Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat. Am J Physiol Regul Integr Comp Physiol. 2008; 295(6): R1782-R1793.