The Influence of Streptozotocin Diabetes on Adrenal Function in Male Rats

Nicola, Alejandro F. De; Fridman, Osvaldo; Castillo, E. J. Del; Foglia, V. G.

doi:10.1055/s-0028-1093620

Cited by 61 publications

(38 citation statements)

References 6 publications

(7 reference statements)

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“…This state can be mimicked in animals by toxic agents, such as streptozotocin (STZ) [12]. In STZ-induced DM a hyperactivity of the HPA axis was described already in 1976 [13]. Diabetes appears to be accompanied by high glucocorticoid levels, lack of circadian rhythmicity and unresponsiveness of the HPA axis to stress stimuli, especially to hypoglycemia [10, 14].…”

Section: Introductionmentioning

confidence: 99%

Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice

et al. 2005

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The present study was aimed at evaluating chronic stress models in mice with special attention to morphine treatment. We hypothesized that repeated periods of drug withdrawal induce chronic stress. To verify this hypothesis, mice were made dependent on morphine and then subjected to several types of repeated withdrawal. Body weight reduction, thymus involution, adrenal gland enlargement and activation of the hypothalamo-pituitary-adrenal axis were used as signs of chronic stress. The changes were compared to those induced by ‘laboratory’ models of chronic stress (2 weeks of repeated restraint or rat exposure) and to a disease model of streptozotocin-induced diabetes mellitus (STZ-DM). Mice were made dependent using increasing doses of morphine three times a day for 3 days (10–20–40 mg/kg s.c.). Thereafter, withdrawal was induced either spontaneously (morphine 40 mg/kg injected at 24- or 72-hour time intervals for 2 weeks) or repeatedly precipitated by naloxone (10 mg/kg s.c.) injected daily 3 h after morphine. The results show that repeated periods of spontaneous drug withdrawal (24 or 72 h) in morphine-dependent mice represent a mild stress load. Repeated withdrawal precipitated by naloxone induced clear chronic stress-like changes. Changes observed in the naloxone-precipitated withdrawal model were even more pronounced than those found in laboratory models, namely repeated restraint or exposure to the rat. The most severe chronic stress state developed in mice during untreated STZ-DM. Thus, naloxone-precipitated withdrawal in mice seems to be an appropriate model of chronic stress.

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Section: Introductionmentioning

confidence: 99%

Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice

et al. 2005

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“…Hypoglycemia is a strong stimulus for HPA axis activation and glucocorticoid production (11,19). Hyperactivity of the HPA axis in experimental STZinduced DM had already been found in 1976 (16). It is also known that patients with both types of DM can have an increased plasma cortisol level (12).…”

mentioning

confidence: 99%

Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats

Zelena¹,

Filaretova²,

Mergl³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Zelena, Dóra, Ludmila Filaretova, Zsuzsa Mergl, István Barna, Zsuzsanna E. Tóth, and Gábor B. Makara. Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats. Am J Physiol Endocrinol Metab 290: E243-E250, 2006. First published September 6, 2005 doi:10.1152/ajpendo.00118.2005.-Diabetes mellitus (DM), as chronic stress activates the hypothalamopituitary-adrenocortical axis. We examined whether arginine vasopressin (AVP) and the hypothalamic paraventricular nucleus (PVN) participate in DM-induced chronic stress symptoms. AVP-deficient Brattleboro or PVN-lesioned Wistar rats were used with heterozygous or sham-operated controls. The rats were studied 2 wk after a single injection of streptozotocin. The appearance of DM (enhanced water consumption and blood glucose elevation) and the chronic stress-like somatic changes (body weight decrease, thymus involution, adrenal gland hypertrophy) were not influenced by the lack of AVP. By contrast, PVN lesion significantly attenuated DM-induced thymus involution and adrenal gland hypertrophy as well as the increase in water consumption. The corticotropin-releasing hormone mRNA in PVN was diminished by DM and elevated by the lack of AVP without interaction. DM elevated the proopiomelanocortin (POMC) mRNA in the anterior lobe of the pituitary. The lack of AVP had no effect, whereas lesioning the PVN significantly diminished the elevation. The elevated basal corticosterone plasma levels detectable in DM were influenced neither by the lack of AVP nor by lesioning the PVN. Thus the lack of AVP had no influence on DM-induced chronic stress symptoms, but lesioning the PVN attenuated part of them. However, the lack of elevation in POMC mRNA after PVN lesion, together with the maintained corticosterone elevation, suggests that direct adrenal gland activation occurs in untreated DM. chronic stress; Brattleboro rats; corticosterone; proopiomelanocortin; corticotropin-releasing hormone; diabetes mellitus; hypothalamopituitary-adrenocortical axis DIABETES MELLITUS (DM) is an endocrine disorder that is quite common in developed countries (17). Inadequate insulin secretion and insulin resistance with inadequate compensatory insulin release are the main reasons for DM development. The use of toxic agents that destroy ␤-cells in the pancreas and lead to insulin deficiency, such as streptozotocin (STZ), produces a model of DM in animals (36). The most frequent symptoms of DM are blood glucose level elevation, polyuria, polydipsia, and weight loss. However, the long-term disorder can cause many other complications, including cardiovascular, cerebrovascular, or renal ones.Long-term DM as a chronic stress may also induce a dysfunction of the hypothalamo-pituitary-adrenocortical (HPA) axis. A tight connection between HPA axis activity and blood glucose regulation is well known (9, 12). The HPA axis is responsible for the production of glucocorticoids, which are important adaptive hormones. Glucocorticoid hormones participate...

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“…Diabetic patients, even those with good glycemic control, demonstrate elevated levels of plasma cortisol and ACTH hormone both before and after dexamethasone suppression tests (Cameron et al 1984, Roy et al 1990). These data demonstrate that both experimental and human diabetes mellitus are accompanied by adrenocortical hyperactivity (De Nicola et al 1976). There have been few studies of adrenal medullary function in diabetic animals.…”

Section: Introductionmentioning

confidence: 93%

“…In STZ-diabetic animal models, adrenalectomy partially restores serum glucose levels and improves diabetesinduced metabolic symptoms (Rodgers et al 1994). Overproduction of adrenal corticosterone is responsible for exacerbating the hyperglycemia in insulin-dependent diabetes mellitus (IDDM) and for causing diabetes-associated growth retardation (De Nicola et al 1976, Rodgers et al 1994, Strack et al 1995. As exogenous corticosterone stimulates food intake and inhibits body-weight gain in adrenalectomized diabetic rats, it has been suggested that glucocorticoids and insulin are interacting reciprocal regulators of energy balance (Strack et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Regulatory effect of experimental diabetes on the expression of endothelin receptor subtypes and their gene transcripts in the rat adrenal gland

Ikeda

Wada²,

Sanematsu³

et al. 2001

Journal of Endocrinology

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Endothelins (ETs) mediate paracrine control of vascular tone and secretion of steroids and catecholamines in the adrenal gland through two ET receptor subtypes, ETA and ETB. The differential distribution and function of these subtypes are responsible for the multiplicity of endothelin actions in this tissue. This study examines the regulatory effects of experimental diabetes on the gene expression, subtype specificity and localization of ET receptor subtypes, ET isopeptides, and endothelinconverting enzyme-1 (ECE-1) in the rat adrenal gland. The densities, pharmacological properties and distribution of ET receptor subtypes ETA and ETB in adrenal glands from streptozotocin-induced diabetic, insulin-treated diabetic and age-matched control rats were investigated, using radioligand receptor binding and autoradiographic techniques. The gene expression of ETA and ETB receptors ET-1, ET-3 and ECE-1 was evaluated using relative multiplex reverse transcription/PCR. The induction of diabetes caused a marked reduction in body weight but no significant change in adrenal gland size. The density of ET receptors was significantly increased in the diabetic rat adrenal gland, mainly because of an increase in the expression of ETB receptors. Insulin treatment normalized the diabetes-induced changes in the expression levels of ET receptor subtypes to control levels. The expression level of ET-1 mRNA was up-regulated, whereas ET-3 mRNA was down-regulated in the diabetic adrenal gland compared with the controls. The ECE-1 mRNA level in the adrenal gland was not altered by the induction of diabetes. Autoradiographic studies showed that ETA and ETB are the predominant receptor subtypes in the adrenal medulla and cortex respectively. These results suggest that ETA and ETB receptors are differentially distributed and regulated in the diabetic rat adrenal gland.

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The Influence of Streptozotocin Diabetes on Adrenal Function in Male Rats

Cited by 61 publications

References 6 publications

Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice

Stress Symptoms Induced by Repeated Morphine Withdrawal in Comparison to Other Chronic Stress Models in Mice

Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats

Regulatory effect of experimental diabetes on the expression of endothelin receptor subtypes and their gene transcripts in the rat adrenal gland

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