Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients Functional Foods in Health and Disease 2017; 7(1): 36-53
Date
02/07/2017Abstract
Background: It is now widely accepted that bariatric surgeries such as Roux-en-Y gastric bypass
(RYGB) and sleeve gastrectomy (SG) can resolve or improve type 2 diabetes mellitus. Postprandial
glucagon-like peptide-1(GLP-1) increases after both RYGB and SG and blockade of the
GLP-1 receptor suppresses the hypoglycemic effect post-operatively. The expedited delivery of
nutrients, including L-glutamine and butyrate, to the distal small intestine and colon, where most
GLP-1–secreting enteroendocrine L-cells are expressed, could explain this increase post-surgery.
Pharmacological treatments that target nutrient-sensing receptors on L-cells may mimic the effects
of bariatric surgeries and may ameliorate deficiencies in gut hormone responses involved in the
regulation of glucose and satiety. In this study, we investigated the effects of the colonic delivery
of L-glutamine and butyrate on GLP-1 secretion and glucose homeostasis in both a pre-clinical
rodent model and clinical type 2 diabetes mellitus (T2DM).
Results: Infusion of 4.4mg of sodium butyrate, compared to saline, into the colon of Zucker
diabetic fatty (ZDF) rats increased GLP-1secretion in response to an intra-duodenal glucose
challenge. In a chronic study, oral dosing of 40mg of sodium butyrate twice a day, formulated as
colon-targeted sustained-release tablets, preserved glucose tolerance and insulin sensitivity in ZDF
rats. In ten T2DM patients requiring oral anti-hyperglycemic agents, infusion of 1g of L-glutamine
into the colon, compared to saline, increased plasma GLP-1 (p=0.017 at 30 min) and insulin
(p<0.01 at 90min; p=0.001 at 120min; AUC p<0.005) after an oral glucose challenge. Similar
Functional Foods in Health and Disease 2017; 7(1): 36-53 Page 37 of 53
infusion with butyrate significantly increased only insulin secretion at 120 min, compared to saline
(p<0.05). Neither agent had an effect on glucose disposal.
Conclusion: Targeted colonic delivery of L-glutamine and butyrate augments secretion of mealstimulated
GLP-1 and insulin; L-glutamine was more efficacious in humans. Such an approach
may be valuable for the management of hyperglycemia in T2DM patients. A chronic clinical
study with colon-targeted sustained-release L-glutamine is required to validate this hypothesis.
Author List
Szewczyk J, Giannone J., Marcuard S., Kindel T, Tso P,Nolan RAuthor
Tammy Lyn Kindel MD, PhD Associate Professor in the Surgery department at Medical College of WisconsinView Online