Combining sitagliptin/metformin with a functional fiber delays diabetes progression in Zucker rats

Reimer, Raylene A.; Grover, Gary J.; Koetzner, Lee; Gahler, Roland J.; Lyon, Michael R.; Wood, Simon

doi:10.1530/joe-13-0484

Cited by 30 publications

(20 citation statements)

References 51 publications

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“…Reimer et al reported a delay in diabetes progression in obese male ZDF rats treated with a viscous and fermentable fiber, PolyGlycopleX (PGX), combined with two drugs, sitagliptin and metformin [38]. Our current study and the Reimer et al study indicated that improved insulin sensitivity is possible in obese ZDF rats and an isolated prebiotic is effective in improving insulin sensitivity.…”

Section: Discussionsupporting

confidence: 63%

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Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat

Goldsmith

Guice

Page

et al. 2016

Molecular Nutrition Food Res

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Scope To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity. Methods and results This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS). ZDF rats fermented RS and RS-rich WG flour to greatest extent among groups. High-RS groups had increased serum glucagon-like peptide 1 (GLP-1) active. Feeding isolated RS showed greater Bacteroidetes to Firmicutes phyla among groups, and rats consuming low RS diets possessed more bacteria in Lactobacillus genus. However, no differences in abdominal fat were observed, but rats with isolated RS had greatest insulin sensitivity among groups. Conclusions Data demonstrated ZDF rats (i) possess a microbiota that fermented RS, and (ii) WG high-RS fermented better than purified RS. However, fermentation and microbiota changes did not translate into reduced abdominal fat. The defective leptin receptor may limit ZDF rats from responding to increased GLP-1 and different microbiota for reducing abdominal fat, but did not prevent improved insulin sensitivity.

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Section: Discussionsupporting

confidence: 63%

“…Reimer et al. reported a delay in diabetes progression in obese male ZDF rats treated with a viscous and fermentable fiber, PolyGlycopleX (PGX), combined with two drugs, sitagliptin and metformin . Our current study and the Reimer et al.…”

Section: Discussionsupporting

confidence: 57%

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat

Goldsmith

Guice

Page

et al. 2016

Molecular Nutrition Food Res

View full text Add to dashboard Cite

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“…Similarly, Matveyenko et al [26] reported a synergistic effect of the combination of both sitagliptin and metformin in controlling body weight in a human islet amyloid polypeptide (HIP) transgenic rat model of type 2 diabetes, rather either agent alone. In addition, Reimer et al [32] reported similar findings in the Zucker diabetic fatty rat model of type 2 DM. These results indicated an effective combination of both sitagliptin and metformin in maintaining body weight in different animal models of type 2 DM.…”

Section: Discussionmentioning

confidence: 70%

The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

Shawky

Morsi

Bana

et al. 2019

Biology

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Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a beneficial class of antidiabetic drugs. However, a major debate about the risk of developing pancreatitis is still existing. The aim of the work was to study the histological and immunohistochemical effects of sitagliptin on both endocrine and exocrine pancreases in a rat model of type 2 diabetes mellitus and to correlate these effects with the biochemical findings. Moreover, a possible synergistic effect of sitagliptin, in combination with metformin, was also evaluated. Fifty adult male rats were used and assigned into five equal groups. Group 1 served as control. Group 2 comprised of untreated diabetic rats. Group 3 diabetic rats received sitagliptin. Group 4 diabetic rats received metformin. Group 5 diabetic rats received both combined. Treatments were given for 4 weeks after the induction of diabetes. Blood samples were collected for biochemical assay before the sacrification of rats. Pancreases were removed, weighed, and were processed for histological and immunohistochemical examination. In the untreated diabetic group, the islets appeared shrunken with disturbed architecture and abnormal immunohistochemical reactions for insulin, caspase-3, and inducible nitric oxide synthase (iNOS). The biochemical findings were also disturbed. Morphometrically, there was a significant decrease in the islet size and islet number. Treatment with sitagliptin, metformin, and their combination showed an improvement, with the best response in the combined approach. No evidence of pancreatic injury was identified in the sitagliptin-treated groups. In conclusion, sitagliptin had a cytoprotective effect on beta-cell damage. Furthermore, the data didn’t indicate any detrimental effects of sitagliptin on the exocrine pancreas.

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“…Reimer et al demonstrated that co-administration of sitagliptin and a viscous fermentable fibre, which is broken down into SCFA, more effectively reduced fasting glycaemia in obese Zucker rats than either treatment alone [53]. Similar results were obtained in the same model when this fibre was combined with metformin or with metformin and sitagliptin [54].…”

Section: Dysbiosis Related To Type 2 Diabetes and Hyperglycaemiamentioning

confidence: 86%

Gut microorganisms as promising targets for the management of type 2 diabetes

et al. 2015

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Each human intestine harbours not only hundreds of trillions of bacteria but also bacteriophage particles, viruses, fungi and archaea, which constitute a complex and dynamic ecosystem referred to as the gut microbiota. An increasing number of data obtained during the last 10 years have indicated changes in gut bacterial composition or function in type 2 diabetic patients. Analysis of this 'dysbiosis' enables the detection of alterations in specific bacteria, clusters of bacteria or bacterial functions associated with the occurrence or evolution of type 2 diabetes; these bacteria are predominantly involved in the control of inflammation and energy homeostasis. Our review focuses on two key questions: does gut dysbiosis truly play a role in the occurrence of type 2 diabetes, and will recent discoveries linking the gut microbiota to host health be helpful for the development of novel therapeutic approaches for type 2 diabetes? Here we review how pharmacological, surgical and nutritional interventions for type 2 diabetic patients may impact the gut microbiota. Experimental studies in animals are identifying which bacterial metabolites and components act on host immune homeostasis and glucose metabolism, primarily by targeting intestinal cells involved in endocrine and gut barrier functions. We discuss novel approaches (e.g. probiotics, prebiotics and faecal transfer) and the need for research and adequate intervention studies to evaluate the feasibility and relevance of these new therapies for the management of type 2 diabetes.

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Combining sitagliptin/metformin with a functional fiber delays diabetes progression in Zucker rats

Cited by 30 publications

References 51 publications

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat

The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

Gut microorganisms as promising targets for the management of type 2 diabetes

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