Oral administration of Lactobacilli engineered to secrete the inactive full-length form of glucagon-like peptide 1 (GLP-11–37) markedly reduces blood glucose levels, according to a new study in rats. The findings have potential implications for the treatment of patients with type 1 diabetes mellitus (T1DM).
Numerous strategies to replace β cells destroyed by autoimmune attack in T1DM have been proposed, including the reprogramming of pancreatic non-β cells and other tissue-specific cells into β cells or cells with insulin-secreting potential. Previously, the researchers showed that genetically engineered commensal bacteria could deliver GLP-11–37 to human intestinal carcinomas and stimulate glucose-responsive insulin secretion. In the current study the investigators tested whether similar bacteria could reduce hyperglycaemia in rats with streptozotocin-induced T1DM. “Our goal was to reprogram rat intestinal cells into glucose-responsive insulin-secreting cells through daily oral administration of GLP-11–37-secreting bacteria,” explain the authors in their report.
Diabetic rats fed GLP-11–37-secreting Lactobacilli daily for 50 days had higher levels of insulin and were more glucose-tolerant following an oral glucose tolerance test than those fed wild-type Lactobacilli; no significant difference was observed in levels of blood glucose and plasma insulin between diabetic rats fed genetically engineered Lactobacilli and nondiabetic control rats. Reduced hyperglycaemia in rats fed GLP-11–37-secreting Lactobacilli was accompanied by the appearance of insulin-secreting intestinal epithelial cells that expressed key β-cell markers (pancreas/duodenum homeobox protein 1, transcription factor MafA and forkhead box protein A2) indicative of reprogramming to an insulin-producing phenotype.
“These results provide evidence of the potential for a safe and effective nonabsorbed oral treatment for diabetes [mellitus] and support the concept of engineered commensal bacterial signalling to mediate enteric cell function in vivo,” the authors conclude in their report.
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03 March 2015
This article was originally published with the incorrect doi. Instead of 10.1038/nrendo.2015.14, the doi should have been 10.1038/nrendo.2015.45. This error has been corrected online in the HTML and PDF versions, and for the print issue.
References
Duan, F. F. et al. Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes. Diabetes 10.2337/db14-0635
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Holmes, D. Genetically engineered Lactobacilli reprogram intestinal cells to secrete insulin and ameliorate hyperglycaemia. Nat Rev Endocrinol 11, 192 (2015). https://doi.org/10.1038/nrendo.2015.45
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DOI: https://doi.org/10.1038/nrendo.2015.45
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