Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gut microbiota requires further investigation.

The purpose of this review is to highlight the role of O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification in metabolic disease states and to summarize current knowledge of how exercise affects this important post-translational signalling pathway. O-GlcNAc modification is an intracellular tool capable of integrating energy supply with demand. The accumulation of excess energy associated with obesity and insulin resistance is mediated, in part, by the hexosamine biosynthetic pathway (HBP), which results in the O-GlcNAcylation of a myriad of proteins, thereby affecting their respective function, stability, and localization. Insulin resistance is related to the excessive O-GlcNAcylation of key metabolic proteins causing a chronic blunting of insulin signalling pathways and precipitating the accompanying pathologies, such as heart and kidney disease. Lifestyle modifications such as diet and exercise also modify the pathway. Exercise is a front-line and cost-effective therapeutic approach for insulin resistance, and recent work shows that the intervention can alter O-GlcNAc gene expression, signalling, and protein modification. However, there is currently no consensus on the effect of frequency, intensity, type, and duration of exercise on O-GlcNAc modification, the HBP, and its related enzymes. On one end of the spectrum, mild, prolonged swim training reduces O-GlcNAcylation, while on the other end, higher intensity treadmill running increases cardiac protein O-GlcNAc modification. Clearly, a balance between acute and chronic stress of exercise is needed to reap the benefits of the intervention on O-GlcNAc signalling.

BackgroundHemoglobin A1c (HbA1c) is the predominant diagnostic tool for diabetes diagnosis and progression. However, it has proven to be insensitive at pre-diabetic threshold values. O-linked-β-N-acetylglucosamine (O-GlcNAc) modification has emerged as a sensitive biomarker. The purpose of this study was to explore the sensitivity of O-GlcNAc expression as a potential marker of early metabolic dysfunction in a young adult population. Healthy, young males (18–35 y) from the Assessing Inherited Metabolic syndrome Markers in the Young study (AIMMY), were divided into low (LH,0.60) or high (HH,1.61) homeostatic model assessment of insulin resistance (HOMA-IR) cohorts.FindingsThe relationships between a panel of anthropometric, metabolic measures and whole blood global protein O-GlcNAc was examined. O-GlcNAc and O-GlcNAc transferase (OGT) levels were quantified by immunoblotting and compared to anthropometric measures: body mass index (BMI), percentage body fat, aerobic fitness, blood glucose, triglycerides, HDL, insulin, and HbA1c. HOMA-IR cohorts showed no differences in BMI, blood glucose or HbA1c, but differed in percent body fat, plasma triglycerides, and circulating insulin. Greater O-GlcNAc expression was observed in the whole blood of HH compared to LH. Moreover, a positive association between HOMA-IR and O-GlcNAc emerged, while no relationship was found between HbA1c and HOMA-IR. This effect was not related to OGT expression.ConclusionsResults indicate that O-GlcNAc has a greater sensitivity to metabolic status compared to HbA1c in this population. O-GlcNAc has the potential to serve as a screening tool for predicting future metabolic disturbances in a young healthy adult population free of any clinically relevant pathologies.Electronic supplementary materialThe online version of this article (doi:10.1186/1758-5996-6-96) contains supplementary material, which is available to authorized users.

Background: Intestinal microbiota are increasingly recognized as potential modifiers of whole‐body energy metabolism. Previous research has described changes in bacterial composition in diabetes; this study examines whether these differences can be altered with lifestyle treatment. Methods: Six‐week‐old diabetic (db/db) and control littermates (db+) were randomized into sedentary or exercise training groups for 6 weeks (n=9‐10/treatment). All animals consumed an identical, chow‐based diet. Exercise consisted of low‐intensity treadmill running (5d/week), and was ceased 48h prior to sacrifice. Cecal matter was collected from individual mice at sacrifice. Total bacterial DNA was extracted and quantified, and bacterial species were detected and profiled using qPCR and group specific primers. Genomic data is reported as the log transformed 16S rRNA copy number normalized for the amount of cecal matter analyzed. Results: Compared to db+ mice, db/db had higher Clostridium Difficile and lower Clostridium Perfringens (P蠄0.05). However, exercise training increased Clos. Perfringens levels in both db+ and db/db (P<0.001); in this way, exercise mitigated the diabetes‐induced reduction in Clos. Perfringens such that exercised db/db mice had levels (5.30 ± 0.09) similar to sedentary db+ (5.19 ± 0.06; P=0.30) and approached that of exercised db+ mice (5.49 ± 0.05; P=0.094). Exercise training independently reduced Bacteroidetes (P=0.009) and increased Clostridium Leptum (P蠄0.05) levels in both db+ and db/db animals. Finally, exercise training increased Bifidobacterium in db+ animals but not db/db mice (P<0.001 for interaction). Conclusion: Diabetes is associated with alterations in the gut bacteria profile, particularly in the Firmicutes species. Exercise training exerts independent effects on bacterial composition in both diabetic and non‐diabetic animals, and may rescue some diabetes‐associated alterations.

Abnormal O‐linked‐β‐N‐acetyl glucosamine glycosylation (O‐GlcNAc) has been increasingly published in relation to several chronic diseases including diabetes. Aims were to examine the relationship between anthropometric and metabolic markers and global protein O‐GlcNAc in whole blood from young adult male subjects participating in the Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY) study. Subjects (n=24, 24±0.8y) were segregated by homeostatic model assessment score (HOMA‐IR); low (LH=0.60) or high (HH=1.61). No difference in body mass index (BMI), glucose or Hemoglobin a1c were found between groups. However, groups differed in % body fat, plasma triglycerides, and circulating insulin. Whole blood O‐GlcNAc levels and OGT modification were quantified by immunoblotting. Results demonstrated an increase in O‐GlcNAc modification in LH compared to HH (p=0.02) along with a strong positive correlation between HOMA‐IR and O‐GlcNAc (r=0.68, p<0.05). This effect was not related to differences in OGT expression. Quantifying differences in O‐GlcNAc levels of whole blood may detect metabolic disturbances present in a young healthy population free of any clinical pathological diagnosis.

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