Microbial tryptophan metabolites modulate L-cell induced GLP-1 secretion to improve glucose homeostasis

2021 ◽  
Author(s):  
Phyllis Phuah ◽  
Sijing Cheng ◽  
Mariana Norton ◽  
Anna Roberts ◽  
Emile Otsubo ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
L Cell ◽  
Tryptophan Metabolites

scholarly journals The role of nutrient sensing in the metabolic changes after gastric bypass surgery

2017 ◽  
Vol 232 (3) ◽  
pp. 363-376 ◽  
Author(s):  
Sandra Steensels ◽  
Matthias Lannoo ◽  
Bert Avau ◽  
Jorien Laermans ◽  
Laurien Vancleef ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Body Weight ◽  
Glucose Homeostasis ◽  
Glucose Transporter ◽  
Nutrient Sensing ◽  
Dependent Manner ◽  
Hormone Release ◽  
L Cell ◽  
Gut Hormone

Taste receptors coupled to the gustatory G-protein, gustducin, on enteroendocrine cells sense nutrients to regulate gut hormone release. During Roux-en-Y gastric bypass (RYGB) surgery, the altered nutrient flow to more distal regions can affect gustducin-mediated gut hormone release and hence energy and glucose homeostasis. We studied the role of gustducin-mediated signaling in the metabolic improvements and intestinal adaptations along the gut after RYGB surgery in wild-type (WT) and α-gustducin−/− (α-gust−/−) mice. RYGB surgery decreased body weight in WT and α-gust−/− mice, whereas food intake was only decreased in WT mice. Pair-feeding to the RYGB group improved glucose homeostasis to a similar extent in WT mice. GLP1 levels were increased in both genotypes, PYY levels in α-gust−/− mice and octanoyl ghrelin levels were not affected after RYGB surgery. In WT mice, nutrients act via α-gustducin to increase L-cell differentiation (foregut) and L-cell number (foregut and hindgut) in a region-dependent manner. In α-gust−/− mice, the effect on gut hormone levels is probably tuned via increased peptide sensor and glucose transporter expression in the Roux limb and increased caecal butyrate and propionate levels in the hindgut that activate free fatty acid receptors. Finally, signaling via α-gustducin plays a role in the increased ion transport of the foregut but not in the improvement in colonic barrier function. In conclusion, RYGB surgery decreased body weight in both WT and α-gust−/− mice. Elevated plasma GLP1 and PYY levels might mediate this effect, although α-gustducin differentially affects several regulatory systems in the foregut and hindgut, tuning gut hormone release.

scholarly journals Ileal microbial shifts after Roux-en-Y gastric bypass orchestrate changes in glucose metabolism through modulation of bile acids and L-cell adaptation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jerry T. Dang ◽  
Valentin Mocanu ◽  
Heekuk Park ◽  
Michael Laffin ◽  
Caroline Tran ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Glucose Tolerance ◽  
Bile Acids ◽  
Cell Density ◽  
Glucose Homeostasis ◽  
Alpha Diversity ◽  
Microbial Composition ◽  
L Cells ◽  
L Cell ◽  
Glucagon Like Peptide 1

AbstractRoux-en-Y gastric bypass (RYGB)-induced glycemic improvement is associated with increases in glucagon-like-peptide-1 (GLP-1) secreted from ileal L-cells. We analyzed changes in ileal bile acids and ileal microbial composition in diet-induced-obesity rats after RYGB or sham surgery to elucidate the early and late effects on L-cells and glucose homeostasis. In early cohorts, there were no significant changes in L-cell density, GLP-1 or glucose tolerance. In late cohorts, RYGB demonstrated less weight regain, improved glucose tolerance, increased L-cell density, and increased villi height. No difference in the expression of GLP-1 genes was observed. There were lower concentrations of ileal bile acids in the late RYGB cohort. Microbial analysis demonstrated decreased alpha diversity in early RYGB cohorts which normalized in the late group. The early RYGB cohorts had higher abundances of Escherichia–Shigella but lower abundances of Lactobacillus, Adlercreutzia, and Proteus while the late cohorts demonstrated higher abundances of Escherichia–Shigella and lower abundances of Lactobacillus. Shifts in Lactobacillus and Escherichia–Shigella correlated with decreases in multiple conjugated bile acids. In conclusion, RYGB caused a late and substantial increase in L-cell quantity with associated changes in bile acids which correlated to shifts in Escherichia–Shigella and Lactobacillus. This proliferation of L-cells contributed to improved glucose homeostasis.

L cell stimulation: a novel strategy for oral peptide delivery in incretin-based diabetes treatment

2020 ◽  
Author(s):  
Ana Beloqui ◽  
Francesco Suriano ◽  
Matthias Hul ◽  
Yining Xu ◽  
Véronique Préat ◽  
...  
Keyword(s):  
Peptide Delivery ◽  
Diabetes Treatment ◽  
Cell Stimulation ◽  
Oral Peptide Delivery ◽  
L Cell ◽  
Novel Strategy

Supplementation with beta-hydroxy-beta-methylbutyrate impacts glucose homeostasis and increases liver size in trained mice

2020 ◽  
Vol 90 (1-2) ◽  
pp. 113-123
Author(s):  
Ines Schadock ◽  
Barbara G. Freitas ◽  
Irae L. Moreira ◽  
Joao A. Rincon ◽  
Marcio Nunes Correa ◽  
...  
Keyword(s):  
Strength Training ◽  
Muscle Mass ◽  
Glucose Homeostasis ◽  
Fasting Blood Glucose ◽  
Hepatic Metabolism ◽  
Mass Gain ◽  
Trained Group ◽  
Tissue Mass ◽  
Liver Size ◽  
Intensive Training

Abstract. β-hydroxy-β-methyl butyrate (HMB) is a bioactive metabolite derived from the amino acid leucine, usually applied for muscle mass increase during physical training, as well as for muscle mass maintenance in debilitating chronic diseases. The hypothesis of the present study is that HMB is a safe supplement for muscle mass gain by strength training. Based on this, the objective was to measure changes in body composition, glucose homeostasis and hepatic metabolism of HMB supplemented mice during strength training. Two of four groups of male mice (n = 6/group) underwent an 8-week training period session (climbing stairs) with or without HMB supplementation (190 mg/kgBW per day). We observed lower body mass gain (4.9 ± 0.43% versus 1.2 ± 0.43, p < 0.001) and increased liver mass (40.9 ± 0.9 mg/gBW versus 44.8 ± 1.3, p < 0.001) in the supplemented trained group compared with the non-supplemented groups. The supplemented trained group had an increase in relative adipose tissue mass (12.4 ± 0.63 mg/gBW versus 16.1 ± 0.88, P < 0.01) compared to the non-supplemented untrained group, and an increase in fasting blood glucose (111 ± 4.58 mg/dL versus 122 ± 3.70, P < 0.05) and insulin resistance (3.79 ± 0.19 % glucose decay/min versus 2.45 ± 0.28, P < 0.05) comparing with non-supplemented trained group. Adaptive heart hypertrophy was observed only in the non-supplemented trained group (4.82 ± 0.05 mg/gBW versus 5.12 ± 0.13, P < 0.05). There was a higher hepatic insulin-like growth factor-1 expression (P = 0.002) in supplemented untrained comparing with non-supplemented untrained group. Gene expression of gluconeogenesis regulatory factors was increased by training and reduced by HMB supplementation. These results confirm that HMB supplementation associated with intensive training protocol drives changes in glucose homeostasis and liver metabolism in mice.

FGF21 improves glucose homeostasis in diabetes-prone NZO mice

2017 ◽  
Vol 12 (S 01) ◽  
pp. S1-S84
Author(s):  
T Laeger ◽  
C Baumeier ◽  
J Würfel ◽  
A Schürmann
Keyword(s):  
Glucose Homeostasis ◽  
Nzo Mice

Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice

2018 ◽  
Vol 239 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Lewin Small ◽  
Henry Gong ◽  
Christian Yassmin ◽  
Gregory J Cooney ◽  
Amanda E Brandon
Keyword(s):  
Glucose Metabolism ◽  
Ambient Temperature ◽  
Fat Mass ◽  
Glucose Homeostasis ◽  
Dietary Intervention ◽  
Whole Body ◽  
Housing Temperature ◽  
Brown Adipose ◽  
Normal Chow ◽  
Obesogenic Diet

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.

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