Animal Models of Type I (Insulin-Dependent) Diabetes Mellitus

Cheţa, D

doi:10.1515/jpem.1998.11.1.11

Cited by 61 publications

(40 citation statements)

References 30 publications

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“…The nonspecific effects of these drugs on the myocardium are not well known. In addition, these animal models of diabetes simulate type 1 diabetes (31), which in the clinical scenario is the least common form in the human population. In this regard, chemically induced models of diabetes do not represent the most appropriate model in which to study the effects of myocardial protection.…”

Section: Fig 2 Representative Western Blots Demonstrating Phosphorymentioning

confidence: 99%

Preconditioning the Diabetic Heart

et al. 2005

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Conflicting evidence exists whether diabetic myocardium can be protected by ischemic preconditioning (IPC). The phosphatidylinositol 3-kinase (PI3K)-Akt pathway is important in IPC. However, components of this cascade have been found to be defective in diabetes. We hypothesize that IPC in diabetic hearts depends on intact signaling through the PI3K-Akt pathway to reduce myocardial injury. Isolated perfused Wistar (normal) and Goto-Kakizaki (diabetic) rat hearts were subjected to 1) 35 min of regional ischemia and 120 min of reperfusion with infarct size determined; 2) preconditioning (IPC) using 5 min of global ischemia followed by 10 min of reperfusion performed one, two, or three times before prolonged ischemia; or 3) determination of Akt phosphorylation after stabilization or after one and three cycles of IPC. In Wistar rats, one, two, and three cycles of IPC reduced infarct size 44.7 ؎ 3.8% (P < 0.05), 31.4 ؎ 4.9% (P < 0.01), and 34.3 ؎ 6.1% (P < 0.01), respectively, compared with controls (60.7 ؎ 4.5%). However, in diabetic rats only three cycles of IPC significantly reduced infarction to 20.8 ؎ 2.6% from 46.6 ؎ 5.2% in controls (P < 0.01), commensurate with significant Akt phosphorylation after three cycles of IPC. To protect the diabetic myocardium, it appears necessary to increase the IPC stimulus to achieve the threshold for cardioprotection and a critical level of Akt phosphorylation to mediate myocardial protection.

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Section: Fig 2 Representative Western Blots Demonstrating Phosphorymentioning

confidence: 99%

Preconditioning the Diabetic Heart

et al. 2005

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“…Although rats daily pretreated with suboptimal doses of insulin tolerated bolus administration of fast-acting insulin without achieving normoglycaemia, the administered insulin caused a more pronounced decrease as compared to the same rats before treatment. Furthermore, the STZ-DM rat differs from other common experimental models of type 1 diabetes, such as pancreatectomized animals, dexamethasone-treated type 1 diabetic rat and alloxan-induced diabetes (Ader et al, 1998;Cheta, 1998;Qi et al, 2004). An explanation to this could be the different origins of the disease and in the different modes of actions of the diabetes-inducing substances (Cheta, 1998;Peschke et al, 2000;Gai et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the STZ-DM rat differs from other common experimental models of type 1 diabetes, such as pancreatectomized animals, dexamethasone-treated type 1 diabetic rat and alloxan-induced diabetes (Ader et al, 1998;Cheta, 1998;Qi et al, 2004). An explanation to this could be the different origins of the disease and in the different modes of actions of the diabetes-inducing substances (Cheta, 1998;Peschke et al, 2000;Gai et al, 2004). To improve the usefulness of the STZ-rat model, it is of vast importance that these differences are taken into account and minimized as much as possible.…”

Section: Discussionmentioning

confidence: 99%

Improvement of insulin response in the streptozotocin model of insulin-dependent diabetes mellitus. Insulin response with and without a long-acting insulin treatment

Nordquist

Sjöquist

2009

Animal

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Streptozotocin-induced diabetes mellitus (STZ-DM) in rats is a model of type 1 diabetes, which is commonly used to study diabetes, but differs from human diabetic pathophysiology in its insulin resistance. An STZ-DM rat can be administered five times the dose of insulin compared to that of a diabetic patient. Thus, attaining normoglycaemia in STZ-DM rats with insulin injections is complicated, and it involves an obvious risk of overdosing before getting a response. This study was designed to investigate whether suboptimal treatment with long-acting insulin restores insulin sensitivity in the STZ-DM rat, and thus an approach to more closely mimic the human condition. Male Sprague-Dawley rats were made diabetic by means of a single intravenous injection of STZ (55 mg/kg body weight (BW)), resulting in an increase in blood glucose (BG) from 6.5 6 0.2 to 22.5 6 1.0 mmol/l ( P < 0.05) within 24 h. After treating the STZ-DM rats with vehicle for 14 days, BG was 26.1 6 1.1 mmol/l, and the response to a single injection of fast-acting insulin (Humalog, 5 IE/kg BW) was a 23% reduction in BG. Thereafter, the rats were treated daily with a suboptimal dose of long-acting insulin for a total of 7 days (Insulatard, 5 IE/kg per day), which resulted in a BG level of 19.4 6 2.7. The response to fast-acting insulin after the suboptimal treatment was a 61% reduction in BG. Thereafter, the animals were vehicle-treated for another 7 days, which resulted in a response to fast-acting insulin similar to the initial values (234%). Furthermore, the group treated with suboptimal doses of long-acting insulin had a longer duration of the reduction in BG (150 min, as opposed to 90 min in the vehicle-treated groups). We conclude that the development of a decreased insulin response occurs rapidly within the first 2 weeks after the onset of diabetes in STZ-DM rats. This leads to a brief and significantly reduced decrease in BG when fast-acting insulin is administered. The insulin response is increased by treatment with suboptimal doses of long-acting insulin, but rapidly decreases again when treatment is withdrawn. Regular administration of suboptimal insulin doses may provide an approach to eliminate the effects of a lowered insulin response.

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“…Streptozotocin (STZ) is well known to destroy the insulinsecreting pancreatic b cells and STZ-treated animals are widely used as a model of type I diabetes that exhibits many of the features seen in human patients with uncontrolled DM, including hyperglycemia, polydipsia and polyuria, and is characterized by severe loss in body weight (Cheta, 1998, Sakai et al, 2003, Tunali & Yanardag, 2013. Hence, the STZ-induced animals can be used to evaluate the skin functional properties of the diabetes patients to some extent.…”

Section: Introductionmentioning

confidence: 99%

The percutaneous permeability and absorption of dexamethasone esters in diabetic rats: a preliminary study

Song

Xiong

et al. 2013

Drug Delivery

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To evaluate the influence of diabetes on the permeation of dexamethasone acetate (DA) and dexamethansone sodium phosphate (DSP), the two major dexamethansone esters in clinical practice, when applied percutaneously, histochemical staining was used to determine the skin morphology; improved Franz diffusion cells and microdialysis were used to assess the percutaneous permeation of DA and DSP in normal and diabetic rats. Histopathological examination showed that the epidermal tissue of diabetic rat was much thinner, the epidermal cell layer was less clear and the stratified arrangement of epidemic cell had almost disappeared and progressive atrophy were developed on the subcutaneous fat. In vitro studies showed that the cumulative and the penetrated DSP amount in Group DM were higher. The mean flux value and the mean depositional amount of Group DM were increased significantly compared to those of Group CTL, whereas the amount of DA penetrating was of no difference. Microdialysis indicated that there was no significant difference between Group CTL and Group DM for all the pharmacokinetic parameters of DA. In contrast, the subcutaneous AUC all values and the C max of DSP were significantly increased compared to the control. In conclusion, diabetic rat skin significantly increased the percutaneous permeation of DSP but had no effect on that of DA. It suggests that patients with diabetes should consider the dose of administration when using DA, DSP or other glucocorticoids topically, as different liposolubilities may play some role in the permeability of these compounds via diabetic skin.

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Animal Models of Type I (Insulin-Dependent) Diabetes Mellitus

Cited by 61 publications

References 30 publications

Preconditioning the Diabetic Heart

Preconditioning the Diabetic Heart

Improvement of insulin response in the streptozotocin model of insulin-dependent diabetes mellitus. Insulin response with and without a long-acting insulin treatment

The percutaneous permeability and absorption of dexamethasone esters in diabetic rats: a preliminary study

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