Secretion of insulinotropic proteins by commensal bacteria: rewiring the gut to treat diabetes.
Here, we show that commensal bacteria can stimulate intestinal epithelial cells to secrete insulin in response to glucose. Commensal strains were engineered to secrete the insulinotropic proteins GLP-1 and PDX-1. Epithelia stimulated by engineered strains and glucose secreted up to 1 ng ml(-1) of insulin with no significant background secretion.
Duan
Faping
F
Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
Curtis
Katherine L
KL
March
John C
JC
D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D054795:Incretins / Q000096:biosynthesis* / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics
D018398:Homeodomain Proteins; D054795:Incretins; D007328:Insulin; D011994:Recombinant Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D052216:Glucagon-Like Peptide 1