High-fat diet and streptozotocin in the induction of type 2 diabetes mellitus: a new proposal

Magalhães, Diego A De; Kume, Willian Tsuyoshi; CORREIA, FRANCYELE S.; Queiroz, Thaís S; Neto, Edgar Wilibaldo Allebrandt; Santos, Maísa Pavani dos; Kawashita, Nair Honda; França, Suélem Aparecida de

doi:10.1590/0001-3765201920180314

Cited by 125 publications

(100 citation statements)

References 25 publications

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“…Streptozotocin (STZ) is a chemical agent that is often used to induce the experimental models of DM through the destruction of the animal pancreatic beta cells with subsequent hyperglycemia. It can be given in combination with a high-fat diet to establish an animal model of type 2 DM [2].…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…Researchers obtained the approval of Falavarjan Branch of Islamic Azad University with ethics code of IR.IAU.FALA.REC.1397.023. In the present study, combination of HFD with STZ was used for diabetes induction in rats (Magalhaes et al, 2019). Combination of HFD with low dose of STZ is known as a T2D model in which HFD induces insulin resistance, and STZ partially destroys the beta cells (Guo et al, 2018).…”

Section: Animals and Animal Treatmentmentioning

confidence: 97%

“…In the present study, combination of HFD with STZ was used for diabetes induction in rats (Magalhaes et al, 2019). Researchers obtained the approval of Falavarjan Branch of Islamic Azad University with ethics code of IR.IAU.FALA.REC.1397.023.…”

Section: Animals and Animal Treatmentmentioning

confidence: 99%

The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats

et al. 2019

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This study aimed to investigate the effect of crocin consumption, high-intensity interval training (HIIT), and low-intensity continuous training (LICT) and their interactive effect on the gene expression of Mfn2 and Drp1 in the skeletal muscle and serum glucose and insulin indices in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. Fifty-six adult rats were divided into eight groups of seven subjects: crocin consumption, HIIT, LICT, HIIT with crocin, LICT with crocin, diabetic control, healthy control, and sham (placebo). At the end of the course (5 months), metabolic indices were measured. Moreover, the Mfn2 and Drp1 gene expression levels in all groups were measured using RT-PCR. The statistical analysis showed that in the exercise training (HIIT and LICT) and the crocin consumption groups, the glucose and insulin indices significantly improved (p = .005). Moreover, in these groups, the levels of gene expression of Mfn2 and Drp1 significantly increased and decreased, respectively (p = .001). Exercise training and crocin consumption appear to, either in combination or individually, have a beneficial effect on mitochondrial dynamics and diabetes by improving the mitochondrial fusion and fission indices (Mfn2 and Drp1), and by modifying the insulin resistance index and glucose homeostasis. Practical applicationsMfn2 and Drp1, as the main regulators of the mitochondrial fusion and fission, play an important role in maintaining mitochondrial dynamics and type 2 diabetes. Thus, the regulation of mitochondrial dynamics is an intricate process that retains the balance between mitochondrial fission and fusion, and any disturbance in this balance can lead to mitochondrial-associated diseases including insulin resistance and T2D. There is evidence that herbal antioxidants Including crocin and exercise training help improve the mitochondrial activity and insulin sensitivity in T2D. Considering the importance of the two Drp1 and Mfn1 genes in the mitochondrial dynamic pathway and coding the proteins that play a key role in relation to T2D, this study primarily examined the interactive effects of endurance training (HIIT and LICT) along with crocin consumption on the expression the genes mentioned above; the results obtained in this study can provide a new approach to the treatment of HFD + STZ-induced diabetic rats. K E Y W O R D Scrocin, Drp1, Mfn2, T2D, training

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“…Male Wistar rats, fed with a high-fat diet and treated with a low dose of STZ (30-40 mg/ kg body weight) is reported to be a reliable model for human type 2 diabetes symptoms, which include peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and hyperglycemia [13,14]. This model, reported to mimic the development of type 2 diabetes and its metabolic features, has been used by various researchers to not only investigate mechanisms involved but also evaluate potential therapies [13,14].…”

Section: Introductionmentioning

confidence: 99%

Anti-hyperglycemic activity of myricetin, through inhibition of DPP-4 and enhanced GLP-1 levels, is attenuated by co-ingestion with lectin-rich protein

et al. 2020

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Dipeptidyl peptidase-4 (DPP-4) is a proteolytic enzyme responsible for the rapid degradation of Glucagon-like peptide 1 (GLP-1) that is required for the secretion of insulin. DPP-4 also influences activation of node like receptor family, pyrin domain containing 3 (NLRP3) inflammasome under diabetic conditions. Although several polyphenols are reported for various bioactivities, they are consumed as part of the food matrix and not in isolation. Horsegram (Macrotyloma uniflorum) is a rich source of myricetin (Myr) (35 μg/g flour), reported for its anti-hyperglycemic effect. In this investigation, we aimed to study the effect of Myr, singly, and in the presence of co-nutrient horsegram protein (HP) on DPP-4 activity and its consequential impact on GLP-1, insulin, and NLRP3 inflammasome in high-fat diet and single low dose streptozotocin (STZ)-induced diabetic male Wistar rats. In diabetic control (DC), the activity of DPP-4 and its expression were higher compared to treated groups. The consequential decrease in the circulating GLP-1 levels in the DC group, but not treated groups, further indicated the effectiveness of our test molecules under diabetic conditions. Specifically, Myr decreased DPP-4 activity and its expression levels with enhanced circulating GLP-1 and insulin levels. Myr administration also resulted in a lessening of diabetes-induced NLRP3 inflammasome activation and enhanced antioxidant enzyme activities. HP also proved to be efficient in reducing elevated blood glucose levels and enhancing antioxidant enzyme activities. However, Myr, in the presence of HP as a co-nutrient, had diminished capacity to inhibit DPP-4 and, consequently, reduced potential in ameliorating diabetic conditions. Myr proved to be a potent inhibitor of DPP-4 in vitro and in vivo, resulting in enhanced circulating GLP-1 and insulin levels, thereby improving diabetic conditions. Though Myr and HP, individually ameliorate diabetic conditions, their dietary combination had reduced efficiency.

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High-fat diet and streptozotocin in the induction of type 2 diabetes mellitus: a new proposal

Cited by 125 publications

References 25 publications

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

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

The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats

Anti-hyperglycemic activity of myricetin, through inhibition of DPP-4 and enhanced GLP-1 levels, is attenuated by co-ingestion with lectin-rich protein

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