Neonatal STZ model of type II diabetes mellitus in the Fischer 344 rat: characteristics and assessment of the status of the hepatic adrenergic receptors

Hemmings, Susan J.; Spafford, David C.

doi:10.1016/s1357-2725(00)00019-4

Cited by 42 publications

(38 citation statements)

References 46 publications

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“…Neonatal insulin-independent DM was provoked by intraperitoneal administration of streptozotocin (STZ) dissolved in 0.9% NaCl solution, pH 4.5, at the dose of 80 mg/kg of body weight in newborn (5-day-old) rats [17]. Animals of control groups received acidified physiological solution.…”

Section: Animalsmentioning

confidence: 99%

Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

Chistyakova

Derkach

et al. 2011

Open Life Sciences

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Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes Abbreviations:AC -adenylyl cyclase; AC system -adenylyl cyclase signaling system; DM -diabetes mellitus; EMD-386088 -5 -c h l o r o -2 -m e t h y l -3 -( 1 , 2 , 3 , 6 -tetrahydro-4-pyridinyl)-1H-indole; GppNHp -b,g-imidoguanosine-5'-triphosphate; 5-HT receptor -5-hydroxytryptamine receptor; hCG -human chorionic gonadotropin; PACAP-38 -pituitary adenylyl cyclase-activating peptide-38. IntroductionHypertension, coronary heart diseases, atherosclerosis, nephropathy, retinopathy, neuropathy, cognitive deficit and disorders of the reproductive system are the most common complications of diabetes mellitus (DM) [1][2][3]. Chronic hyperglycemia is quite often an important contributing factor in the development of these complications. Many hormone-and growth factorregulated signaling pathways, such as the adenylyl cyclase (AC) signaling system, phospholipase C/protein kinase C signaling system and the cascade of mitogenactivated protein kinases are implicated in the regulation of the cardiovascular, nervous and reproductive systems and aberration of their functional activity in DM may contribute to complications of this disease [4][5][6][7][8]. It has been shown that in experimental types 1 and 2 DM the functional activity of hormone-sensitive AC system in the skeletal muscles, myocardium, testis, ovaries, uterus and brain of diabetic rats and the sensitivity of this system to hormones regulating AC activity are changed in tissue-and hormone-specific manner [6][7][8][9][10][11][12].The most significant changes of hormonal sensitivity of AC system were found in the myocardium, testis and Abstract:The changes in hormone-regulated adenylyl cyclase (AC) signaling system implicated in control of the nervous, cardiovascular and reproductive systems may contribute to complications of diabetes mellitus (DM). We investigated the functional state of AC system in the brain, myocardium, ovary and uterus of rats with neonatal DM and examined the influence of intranasally administered insulin on the sensitivity of this system to biogenic amines and polypeptide hormones. The regulatory effects of somatostatin and 5-HT 1B R-agonist 5-nonyloxytryptamine acting via G i protein-coupled receptors were significantly decreased in DM and partially restored in insulin-treated rats. The effects of hormones, activators of AC, are changed in tissue-and receptorspecific manner, and intranasal insulin restored the effects rather close to the level in control. In insulin-treated non-diabetic rats, AC stimulating effects of isoproterenol and relaxin in the myocardium and of human chorionic gonadotropin in the ovaries were decreased, while the effects of hormones, inhibitors of AC, were increased. These data indicate that with intranasal insulin, G i protein-mediated signaling pathways continue to gain strength. The obtained data on the influence of hormones on AC system in the brain, myocardium, ovary and uterus allow looking anew into the mechanisms of therapeutic ...

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Section: Animalsmentioning

confidence: 99%

Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

Chistyakova

Derkach

et al. 2011

Open Life Sciences

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“…The animals were successively intragastric administration with fat milk for 20 days and abdominal cavity injection with streptozotocin (STZ) 45 mg/kg. After fasting 72 h, those with the blood glucose over 11 mmol/L were taken as successful modeling and involved in the T2D group [27,28]. Sample preparation was carried out in 'Section 2.3' and a 5 L aliquot of the reconstructed solution was injected into the UPLC-Q-TOF/MS system.…”

Section: Metabolic Profiling Analysis Of T2d Rat Livermentioning

confidence: 99%

Method for liver tissue metabolic profiling study and its application in type 2 diabetic rats based on ultra performance liquid chromatography–mass spectrometry

Huang

Yin

Wang

et al. 2011

Journal of Chromatography B

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“…However, at the early stages of development of rats, the first week after birth, a partial restoration of insulin-producing function of B cells can occur due to their regeneration. 33 As a rule, 50-70 % of infant rats treated with STZ show signs of T2DM on reaching the age of 2.5-3 months. 34 In our experiments, 70% of 3-month old STZ-treated rats had glucose tolerance, as assessed in the glucose tolerance test (GTT) using i.p.…”

Section: Neonatal Model Of Type 2 Diabetesmentioning

confidence: 99%

“…The diabetic animals had long-term moderate hyperglycemia (fasting blood glucose level was no higher than 7 mM) and slightly decreased plasma insulin level, which agrees well with the corresponding parameters of the rats with a neonatal model of T2DM obtained by others. 33,34 In GTT, 120 min. after glucose load, the concentration of glucose in the blood of control rats (Group C) reached normal levels.…”

Section: Characteristics Of Neonatal Diabetesmentioning

confidence: 99%

A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

et al. 2011

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Type 2 diabetes mellitus (T2DM) is associated with cognitive impairments. However, their causal factors and the approaches to be used in their treatment have not been fully clarified and further study is needed. The aim of this work was to study the effect of intranasal insulin (I-I) on cognitive functions in rats with experimental T2DM. Neonatal rats (5 days old) were treated with an intraperitoneal (i.p.) administration of a single dose of streptozotocin (STZ) (80 mg/kg i.p.) which in adult animals leads to impairment of glucose tolerance and mild hyperglycemia, typical of T2DM. The insulin receptor binding in the synaptosomal and liver membranes was evaluated with [ 125 I]-insulin, and the insulin receptor substrate 2 (IRS2) expression in the brain was estimated by RT-PCR. Daily I-I (0.48 IU/day) or placebo were delivered to diabetic and non-diabetic rats during a week before and the 39 days of cognition experiments. Spatial memory and learning were studied in a Morris water-maze (MWM) test. The MWM test showed that, in the case of diabetic rats, the latent period for finding the platform (escape latency) and the swimming path length were increased, and the number of annulus crossings decreased compared with control (P<0.05). I-I normalized cognitive functions in diabetic rats but had no effect on those of non-diabetic animals. Specific insulin binding in the liver of diabetic rats was decreased, indicating peripheral insulin resistance, but changed very little in the brain. In the hypothalamus of diabetic rats, but not in the cortex and the olfactory bulbs, the expression of IRS2 was reduced by 68% compared with control and was restored after I-I delivery. Rats with neonatal T2DM had cognitive deficit likely associated with impaired IRS2-mediated signaling pathways in the diabetic brain and eliminated by I-I treatment.

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Neonatal STZ model of type II diabetes mellitus in the Fischer 344 rat: characteristics and assessment of the status of the hepatic adrenergic receptors

Cited by 42 publications

References 46 publications

Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

Method for liver tissue metabolic profiling study and its application in type 2 diabetic rats based on ultra performance liquid chromatography–mass spectrometry

A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

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