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Posted June 29, Share this post Link to post Share on other sites. Belfrybat Plasma DPP4 activity was measured according to Kirino et al. A clinical chemistry panel was analyzed in serum and included: blood urea nitrogen, glucose, electrolytes, creatinine, alkaline phosphatase, aspartate aminotransferase ALT , alanine aminotransferase AST , and bilirubin.
Following the cardiac blood draw, one kidney, one lobe of the liver, and a section of the distal ileum were snap—frozen for later DPP4 analysis DPP4 activity in kidney and Dpp4 mRNA levels according to our previous work Reimer et al. The pancreas was serial sectioned twice at approximately five microns and either stained with hematoxylin and eosin or immunohistochemically stained with a mouse antibody against rat insulin according to our previous work Grover et al.
The percent islet area containing insulin-positive cells was determined by morphometric evaluation using the Image-Pro Plus IPP software system.
One liver lobe was snap—frozen for the determination of lipid content with Sudan Black staining. Histopathology scoring was the same as described earlier for the pancreas. Microbial profiling was performed according to our previous work Bomhof et al. Expression of the tight junction-associated genes, zona occludens-1 ZO1 and occludin, as well as proglucagon was analyzed according to our standard real-time PCR protocol Bomhof et al. When a significant interaction effect was identified indicating that the influence of the diet on the outcome of interest was dependent on the presence of the drug or vice versa , a one-way ANOVA with Tukey's multiple comparison post hoc test was used to assess the differences between the individual groups.
For parameters where repeated measurements were taken over time i. Food intake was lower in all groups compared with C Table 1. There were no differences in lean mass between groups. Citation: Journal of Endocrinology , 3; Blood glucose was also measured in the fed state on a weekly basis Fig. AUC for glucose and all regulators of eating behavior is provided in Supplementary Table 1 , see section on supplementary data given at the end of this article. The brown-stained tissue is positive for insulin-containing cells within the pancreas.
Bifidobacterium were very low across all groups. Dietary recommendations for the management of diabetes encourage individuals at risk for or diagnosed with diabetes to achieve dietary fiber intake at least at the level suggested for the general population American Diabetes Association et al. Viscous dietary fiber, in particular, has been shown to slow glucose absorption from the small intestine and may be particularly relevant Vuksan et al. In addition to lifestyle modification, many newly diagnosed type 2 diabetes patients are prescribed MET as a first-line antihyperglycemic agent Papanas et al.
Our findings suggest that the actions of these medications can be augmented with the functional dietary fiber PGX. Overt hyperglycemia typically develops in the ZDF rat by 10—12 weeks of age Peterson et al. Interestingly, the PGX alone group maintained lower fed and fasted glucose concentrations throughout the 6 weeks compared with control and the two drug monotherapies but did eventually develop diabetes by the end of the study, suggesting that this functional fiber worked as well, if not slightly better than currently approved diabetes medications in lowering glycemia in this model at the doses selected.
In addition to weekly fasted and fed blood glucose measurements, we also assessed HbA1c. We examined several potential mechanisms by which the improvements in glycemia might take place.
Firstly, changes in weight gain and body composition could explain some of the improvements. Adipose tissue mass, and perhaps more importantly the inflammatory cytokines released from adipose tissue, have been implicated in insulin resistance Gutierrez et al. Although we did not perform euglycemic hyperinsulinemic clamps to assess insulin sensitivity directly, we do have indirect indicators of improved insulin sensitivity. DPP4 is a serine protease that inactivates polypeptides such as GLP1 and is expressed on the surface of various types of cells, including the small intestine, kidney, liver, and in a soluble form in plasma Kirino et al.
While it is not clear whether DPP4 activity plays a role in the onset or progression of diabetes, there is some evidence to suggest that inhibiting DPP4 with sitagliptin may exert additional actions at the level of the L cell by acting as a GLP1 secretagogue Sangle et al. This is consistent with our data showing no reduction in DPP4 activity or expression in rats treated with MET compared with control rats. Gut microbiota have been implicated in the development and maintenance of obesity in part through a contribution to low-grade inflammation or metabolic endotoxemia Cani et al.
Because LPS leaks into circulation via a compromised gut barrier Cani et al. Changes in barrier function and other host metabolic responses can occur in response to an alteration in the composition of the microbiota Cani et al. Obesity has been characterized by an increase in the proportion of Firmicutes and reduction in Bacteroidetes Ley et al.
All treatments in our study reduced C. We also saw a marked increase in Enterobacteriaceae with PGX. The significance of this shift is perhaps made clear by the findings of Zhang et al.
Gastric bypass surgery, by design, results in the presentation of nutrients to more distal segments of the intestine. It is plausible that PGX, a functional fiber with a level of viscosity that is higher than any currently known individual polysaccharide, could create a luminal environment where nutrients are absorbed more distally.
It is also plausible that the end-products of microbial fermentation of PGX, short-chain fatty acids SCFA , affect the composition of gut microbiota in these rats and the secretion of gut satiety hormones Wichmann et al. Given that fermentation of fibers can improve gut barrier function Lappi et al. In this study, we were able to confirm the previously demonstrated reduction in total cholesterol with PGX Grover et al.
Hepatic steatosis is the first hit in a cascade of non-alcoholic fatty liver disease that can progress to fibrosis and end-stage liver disease Parnell et al. Given the recent demonstration that sitagliptin is able to inhibit liver fibrosis in rats Kaji et al. Effective management of obesity and type 2 diabetes requires an integrated approach that considers patient characteristics and available pharmacological options Stein et al. It is common to use a combination of medications to optimize glycemic control and patient outcomes in the context of metabolic disease.
The impact that lifestyle, and specifically dietary factors, might have on the action of those medications has received much less attention. Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.
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