The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes

Wei, Michael C.; Ong, Leslie; Smith, Maree T.; Ross, F. B.; Schmid, Katrina L.; Hoey, Andrew; Burstow, Darryl J.; Brown, Lindsay

doi:10.1046/j.1444-2892.2003.00160.x

Cited by 191 publications

(137 citation statements)

References 22 publications

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“…The most widely used rodent model of type 1 diabetes involves the destruction of ␤-cell function by STZ administration. A high single dose of STZ causes rapid destruction of the ␤-cells, resulting in persistent hypoinsulinemia and hyperglycemia accompanied by weight loss (24,64). By comparison, multiple low-dose injections of STZ act by a slower immune-mediated mechanism that may better mimic the development of human type 1 diabetes subjects (32,35).…”

Section: Discussionmentioning

confidence: 99%

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

Soares

Carvalho

Veiga

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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-Type 1 diabetes subjects are characterized by impaired direct pathway synthesis of hepatic glycogen that is unresponsive to insulin therapy. Since it is not known whether this is an irreversible defect of insulin-dependent diabetes, direct and indirect pathway glycogen fluxes were quantified in streptozotocin (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied at 18 days post-STZ treatment. One group was administered I-SC and another I-IP as two daily injections of short-acting insulin at the start of each light and dark period for days 9 -18. A third group did not receive any insulin, and a fourth group of nondiabetic rats was used as control. Glycogen synthesis via direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were determined over the nocturnal feeding period using deuterated water. Direct pathway was residual in STZ rats, and glucokinase activity was also reduced significantly from control levels. Insulin administration restored both net glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic control levels and improved the lipogenic pathway despite an inefficient normalization of the gluconeogenic pathway. We conclude that the reduced direct pathway flux is not an irreversible defect of insulindependent diabetes. indirect pathway; 2 H-nuclear magnetic resonance; glucokinase; de novo lipogenesis TYPE 1 DIABETES IS CHARACTERIZED by significant alterations in hepatic carbohydrate and lipid metabolism resulting from insulin insufficiency, and impairment of postprandial glycogen synthesis is among the best studied of these characteristics. Hepatic glycogen is synthesized via two pathways, the classical direct pathway from intact glucose units and the indirect pathway by which glucose is first metabolized to 3-carbon intermediates (pyruvate and further to lactate), followed by gluconeogenic resynthesis into glucose 6-phosphate (G6P) (Fig.

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Section: Discussionmentioning

confidence: 99%

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

Soares

Carvalho

Veiga

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Unraveling which are the most critical mechanisms is unlikely to be achieved in studies limited to the clinically observable retinal changes in human DR. Far more detailed and invasive studies are required, preferably in a readily available animal model. 4 The streptozotocin-induced diabetes in rats shows many of the retinal alterations associated with human DR. [5][6][7] Therefore, this model could be a useful tool for studying the pathogenic mechanisms involved in DR, as well as for developing new therapeutics.…”

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confidence: 99%

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Fernandez

Sande

Chianelli

et al. 2011

The American Journal of Pathology

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Diabetic retinopathy is a leading cause of acquired blindness. Available treatments are not very effective. We investigated the effect of a weekly application of retinal ischemia pulses (ischemic conditioning) on retinal damage induced by experimental diabetes. Diabetes was induced by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 minutes; this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, whereas the contralateral eye was submitted to a sham procedure. Diabetic retinopathy was evaluated in terms of i) retinal function (electroretinogram and oscillatory potentials), ii) integrity of blood-retinal barrier (by albumin-Evans blue complex leakage and astrocyte glial fibrillary acidic protein IHC), iii) optical and electron microscopy histopathologic studies, and iv) vascular endothelial growth factor levels (using Western blot analysis and IHC). Brief ischemia pulses significantly preserved electroretinogram a-and b-wave and oscillatory potentials, avoided albumin-Evans blue leakage, prevented the decrease in astrocyte glial fibrillary acidic protein levels, reduced the appearance of retinal edemas, and prevented the increase in vascular endothelial growth factor levels induced by experimental diabetes. When the application of ischemia pulses started 6 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies for diabetic retinopathy treatment.

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“…Typically, young adult rats (8-12 weeks of age when diabetes is induced) are used to investigate the complications of DM and its treatment (34,39,40) . Independently, older Wistar rats are known to develop the metabolic syndrome/insulin resistance with age as visceral and retroperitoneal fat mass increases (41,42) .…”

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confidence: 99%

Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats

et al. 2016

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Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P < 0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus.

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The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes

Cited by 191 publications

References 22 publications

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

Induction of Ischemic Tolerance Protects the Retina From Diabetic Retinopathy

Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats

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