Bethany Cummings

Bethany Cummings DVM, PhD, Professor, Department of Surgery, School of Medicine, Department of Molecular Biosciences, Weill School of Veterinary Medicine, University of California, Davis

Research Description: My laboratory has long studied the pathophysiology and treatment of type 2 diabetes. Using mouse models along with molecular biology, biochemistry, genomics, and pharmacology, we investigate the molecular basis of metabolic disease and look for new therapeutic targets. Our work has helped clarify how bariatric surgery improves glucose regulation and islet function, particularly through bile acids and glucagon-like peptide-1 (GLP-1). We showed that the bile acid receptor TGR5 contributes to the improvements in glycemic control and bile acid metabolism seen after bariatric surgery in mice. Building on this, we explored which bile acid metabolic pathways could be targeted to improve diabetes treatment, and found that dietary fiber supplementation and fecal microbiota transplantation increase bacterial bile acid metabolism in the gut through a non-canonical pathway. In addition, using a humanized, inducible, β-cell-specific GLP-1 receptor (GLP-1R) knockout mouse, we found that bariatric surgery improves islet function and stimulates α-cell GLP-1 production by enhancing β-cell GLP-1R signaling. In later work applying lessons from bariatric surgery to GLP-1 pharmacology, we identified 14-3-3ζ as a novel regulator of GLP-1R agonist function and of the α-cell endocrine profile of islets.

Selected relevant publications (SDRC members in BOLD):

  1. Shishani R, Moreno R, Agabao-Tucker ME, Dinglasan SE, Bustamante JM, Eddy E, Jackson A, Reuter MA, Hon MK, Huising MO, Lim GE, Cummings BP. β-cell 14-3-3-ζ and sex are key regulators of α-cell form and function. Endocrinology. 2026 Sep 29;167(11):bqag098. doi: 10.1210/endocr/bqag098. PMID: 42644279; PMCID: PMC13621187.

  2. Holter MM, Saikia M, Cummings BP. α-cell paracrine signaling in the regulation of β-cell insulin secretion. Frontiers in Endocrinology. 2022; 13:934775. PMC9360487

  3. Holter MM, Phuong DJ, Lee I, Saikia M, Weikert L, Anderson ET, Fu Q, Zhang S, Sloop KW, Cummings BP. 14-3-3ζ contributes to the effect of enhanced β-cell GLP-1 receptor signaling to alter α-cell proglucagon processing. Science Advances. 2022; 8:eabn3773. PMC9307243