Nongenetic mouse models of non—insulin-dependent diabetes mellitus

Luo, Jian; Quan, Josephine; Tsai, Joyce; Hobensack, C.; Sullivan, Cynthia S.; Hector, Richard F.; Reaven, Gerald M.

doi:10.1016/s0026-0495(98)90027-0

Cited by 202 publications

(185 citation statements)

References 14 publications

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“…Impaired insulin secretion because of insufficient ␤ cell function is a key feature of type 2 diabetes (1). In this study, mice were fed HFD for 8 weeks, followed by injection of a moderate dose of STZ to induce hyperglycemia (32). A time-course study indicated that blood glucose levels were similar in both groups (WT and DP-IV Ϫ͞Ϫ ) during the first 2 weeks after STZ injection.…”

Section: Dp-iv ؊͞؊mentioning

confidence: 97%

Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance

Conarello

Ronan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

328

223

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Dipeptidyl peptidase IV (DP-IV), a member of the prolyl oligopeptidase family of peptidases, is involved in the metabolic inactivation of a glucose-dependent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), and other incretin hormones. Here, we investigated the impact of DP-IV deficiency on body weight control and insulin sensitivity in mice. Whereas WT mice displayed accelerated weight gain and hyperinsulinemia when fed a high-fat diet (HFD), mice lacking the gene encoding DP-IV (DP-IV ؊͞؊ ) are refractory to the development of obesity and hyperinsulinemia. Pair-feeding and indirect calorimetry studies indicate that reduced food intake and increased energy expenditure accounted for the resistance to HFD-induced obesity in the DP-IV ؊͞؊ mice. Ablation of DP-IV also is associated with elevated GLP-1 levels and improved metabolic control in these animals, resulting in improved insulin sensitivity, reduced pancreatic islet hypertrophy, and protection against streptozotocin-induced loss of ␤ cell mass and hyperglycemia. Together, these observations suggest that chronic deletion of DP-IV gene has significant impact on body weight control and energy homeostasis, providing validation of DP-IV inhibition as a viable therapeutic option for the treatment of metabolic disorders related to diabetes and obesity.

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Section: Dp-iv ؊͞؊mentioning

confidence: 97%

Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance

Conarello

Ronan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

328

223

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“…Previous studies have shown that low-dose STZ injection leads to the partial destruction of pancreatic beta cells and a high-fat diet (HFD) induces insulin resistance in rodents [21][22][23]. The degree of beta cell destruction and insulin resistance can be adjusted by dosage, duration and condition of STZ injection and HFD feeding [11,24].…”

Section: Introductionmentioning

confidence: 99%

“…The degree of beta cell destruction and insulin resistance can be adjusted by dosage, duration and condition of STZ injection and HFD feeding [11,24]. The effects of various glucose-lowering drugs (sulfonylurea, metformin, thiazolidinedione etc) have been examined in mice treated with low-dose STZ and HFD as a model of type 2 diabetes [22,23]. In the present study, we too generated a mouse model mimicking human type 2 diabetes using low-dose STZ and HFD to examine the effect of leptin infusion.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and a high-fat diet

et al. 2009

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Aims/hypothesisWe have previously demonstrated the therapeutic usefulness of leptin in lipoatrophic diabetes and insulin-deficient diabetes in mouse models and could also demonstrate its dramatic effects on lipoatrophic diabetes in humans. The aim of the present study was to explore the therapeutic usefulness of leptin in a mouse model of type 2 diabetes with increased adiposity. Methods To generate a mouse model mimicking human type 2 diabetes with increased adiposity, we used a combination of low-dose streptozotocin (STZ, 120 μg/g body weight) and high-fat diet (HFD, 45% of energy as fat). Recombinant mouse leptin was infused chronically (20 ng [g body weight] −1 h −1 ) for 14 days using a mini-osmotic pump. The effects of leptin on food intake, body weight, metabolic variables, tissue triacylglycerol content and AMP-activated protein kinase (AMPK) activity were examined. Results Low-dose STZ injection led to a substantial reduction of plasma insulin levels and hyperglycaemia. Subsequent HFD feeding increased adiposity and induced insulin resistance and further augmentation of hyperglycaemia. In this model mouse mimicking human type 2 diabetes (STZ/HFD), continuous leptin infusion reduced food intake and body weight and improved glucose and lipid metabolism with enhancement of insulin sensitivity. Leptin also decreased liver and skeletal muscle triacylglycerol content accompanied by an increase of α2 AMPK activity in skeletal muscle. Pairfeeding experiments demonstrated that leptin improved glucose and lipid metabolism independently of the food intake reduction. Conclusions/interpretation This study demonstrates the beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity, indicating the possible clinical usefulness of leptin as a new glucose-lowering drug in humans.

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“…It has been found that DPPH * can oxidize cysteine, glutathione, ascorbic acid, tocopherol and polyhydroxy aromatic compounds [56]. ABTS*+produce more powerful free radicals than DPPH * radicals and the reactions with ABTS *+ radicals involve a single electron transfer process [57]. The principle of ABTS *+ assay is that the preformed radical monocation of ABTS *+ is generated by oxidation of ABTS *+ with potassium per sulfate and is reduced in the presence of such hydrogen-donating antioxidants.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Screening and Evaluation of in Vitro Antioxidant Potential of Immature Palmyra Palm (Borassus Flabellifer Linn.) Fruits

Renuka

Devi

Subramanian

2018

Int J Pharm Pharm Sci

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Objective: The present study was aimed to evaluate the in vitro antioxidant properties of immature Palmyra palm fruits which have been traditionally used for the treatment of diabetes. The qualitative phytochemical screening and quantitative estimation of total phenolic and flavonoids contents in the ethanolic extract were performed to substantiate the antioxidant and medicinal claims. Methods:Immature palmyra palm fruits were collected, authenticated, dried and powdered in an electrical grinder. The powdered fruits were delipidated in petroleum ether and soxhilation using ethanol to extract the active ingredients. Qualitative phytochemical screening, total phenolic and flavonoid contents were carried out by established methods. The in vitro antioxidant potentials were performed by diphenyl-2-picrylhydrazyl, azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, nitric oxide and superoxide anion scavenging assays. Results:The phytochemical screening showed the presence of alkaloids, flavonoids, glycosides, saponins, tannins, phytosterols, triterpenoids and phenols in the immature palmyra palm fruits extract. The total phenolic and flavonoid contents in the fruits extract was found to be 104.00±0.02 μg gallic acid equivalents/100 mg of fruits extract and 98.45±0.03 μg quercetin equivalents/100 mg, respectively. The percentage inhibition of DPPH radicals range from 35 to 70% at a concentration ranges from 200-1000μg/ml. Similarly, the percentage of inhibition of ABTS radicals was found to be in the range of 40 to 75.5%. The nitric oxide scavenging activity of the fruits extract ranges from 45 to 76% whereas the superoxide radical scavenging activity ranges from 43 to 83%. Conclusion:The observed significant free radical scavenging activity along with increased total phenolic as well as flavonoid contents suggest that the immature fruits may be considered as a potential source for the identification of pharmacologically active phytochemicals capable of controlling oxidative stress.

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Nongenetic mouse models of non—insulin-dependent diabetes mellitus

Cited by 202 publications

References 14 publications

Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance

Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance

Beneficial effects of leptin on glycaemic and lipid control in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and a high-fat diet

Phytochemical Screening and Evaluation of in Vitro Antioxidant Potential of Immature Palmyra Palm (Borassus Flabellifer Linn.) Fruits

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