Gut Microbiota and Glucose Homeostasis
Affiliation
Department of Diabetes Technology, Tohoku University of Graduate School of Biomedical Engineering, 6-6-11, Aramakiaza, Aoba, Aoba-ku, Sendai, Miyagi 980-8579, Japan
Corresponding Author
Katsunori Nonogaki MD, PhD, Professor, Department of Diabetes Technology, Tohoku University of Graduate School of Biomedical Engineering, 6-6-11, Aramakiaza, Aoba, Aoba-ku, Sendai, Miyagi 980-8579, Japan, Tel: +81-22-795-3865; Fax: +81-22-795-3865; E-mail: katsu@trc.med.tohoku.ac.jp
Citation
Nonogaki, K., et al. Gut Microbiota and Glucose Homeostasis. (2015) J Diabetes Obes 2(4): 1.
Copy rights
© 2015 Nonogaki, K. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Introduction
The involvement of gut microbiota in type 2 diabetes has been recognized[1,2]. Several Clostridium or lactobacilli species are reportedly enriched in type 2 diabetes[1,2]. A study by Forslund et al, showed that gut microbes mediate the therapeutic effects of metformin through certain types of short-chain fatty acid production[3]. Gut microbiota may therefore influence insulin sensitivity. Serum metformin levels of type 2 diabetes patients are positively correlated with Escherichia abundance, whereas they are negative correlation with Intestinibacter abundance[3].
Serotonin (5-hydroxytryptamine, 5-HT) is mainly synthesized, stored, and released from enterochromaffin cells within mucosal epithelia of the gut[4]. Gut microbes regulate 5-HT levels in the colon and blood. Spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells, which supply 5-HT to the mucosa, lumen, and circulating platelets[4]. The microbiota-dependent changes in gut 5-HT impact gastrointestinal motility and platelet function[4].
5-HT1B and 5-HT4 receptors, which are distributed in the enteric nervous system and smooth muscle in the gut, may be involved in the gut-mediated glucose homeostasis[5,6]. Pharmacologic stimulation of serotonin 5-HT1B or 5-HT4 receptors increases plasma active glucagon-like-peptide-1 levels independently of feeding and improves glucose tolerance under the dipeptidyl peptidase-4 inhibition in mice[5,6]. Although it remains unclear whether gut microbiota influence insulin secretion, the gut microviota-5-HT axis may be a novel therapeutic target for type 2 diabetes in future.
References
- 1. Qin, J., Li. Y., Cai, Z., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. (2012) Nature 490(7418): 55-60.
- 2. Karlsson, F.H., Tremaroli, V., Nookaew, I., et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. (2013) Nature 498(7942): 99-103.
- 3. Forslund, K., Hildebrand, F., Nielsen, T., et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. (2015) Nature.
- 4. Yano, J., Yu, K., Donaldson, G.P., et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. (2015) Cell 161(2): 264-276.
- 5. Nonogaki, K., Kaji, T. Pharmacological stimulation of serotonin 5-HT1B receptors enhances increases in plasma active glucagon-like peptide-1 levels induced by dipeptidyl peptidase-4 inhibition independently of feeding in mice. (2015) Diabetes Metab 41(5): 425-428.
- 6. Nonogaki, K., Kaji, T. Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active GLP-1 levels and glucose tolerance in mice. (2015) Diabetes Res Clin Pract.