Functional and Molecular Aspects of Glucocorticoids in the Endocrine Pancreas and Glucose Homeostasis

Rafacho, Alex; Boschero, Antônio Carlos; Ortsäter, Henrik

doi:10.5772/50233

Cited by 6 publications

(11 citation statements)

References 103 publications

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“…Short-term treatment with dexamethasone is a valuable tool to stress and challenge the glucose homeostasis once GCs exert diabetogenic effects (e.g., hyperglycemia, hyperinsulinemia, hyperglucagonemia, hypertriacylglyceridemia, insulin resistance) in both human and rodents [20][21][22]. All of these metabolic alterations, except for hyperglucagonemia (not quantified in the current study), were confirmed in the dexamethasone-treated rats (DEX) while rats with reduced ovary function (VCD + DEX) did not exhibit exacerbation of such parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Glucocorticoids (GCs) are among the most effective diabetogenic hormones and there is substantial evidence with humans and rodents treated with synthetic GC (e.g., dexamethasone) in different contexts (acutely with high doses or chronically with low doses) demonstrating its impact on glucose and lipid metabolism such glucose intolerance, reduction of insulin sensitivity, elevation in blood glucose, plasma insulin and triacylglycerol levels, etc. (reviewed in [20][21][22]). We have a well-established model of rats treated with dexamethasone that exhibit prediabetes like phenotype (e.g., glucose intolerance, insulin resistance, elevation in blood glucose, plasma insulin, glucagon, tryacilglycerol levels) [23][24][25], which serves as a good model to stress the glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment

Battiston

Santos

Barbosa

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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4-vinilcyclohexene diepoxide (4-VCD) causes premature ovarian failure and may result in estrogen deficiency, characterizing the transition to estropause in rodents (equivalent to menopause in women). Estropause/menopause is associated with metabolic derangements such as glucose intolerance and insulin resistance. Glucocorticoids (GCs) are known to exert diabetogenic effects. Thus, we aimed to investigate whether rats with premature ovarian failure are more prone to the diabetogenic effects of GC. For this, immature female rats received daily injections of 4-VCD [160mg/kg body weight (b.w.), intraperitoneally (i.p.)] for 15 consecutive days, whereas control rats received vehicle. After 168days of the completion of 4-VCD administration, rats were divided into 4 groups: CTL-received daily injections of saline (1mL/kg, b.w., i.p.) for 5days; DEX-received daily injections of dexamethasone (1mg/kg, b.w., i.p.) for 5days; VCD-treated as CTL group; VCD+DEX-treated as DEX group. Experiments and euthanasia occurred one day after the last dexamethasone injection. 4-VCD-treated rats exhibited ovary hypotrophy and reduced number of preantral follicles (p<0.05). Premature ovarian failure had no impact on the body weight gain or food intake, but both were reduced by the effects of dexamethasone. The increase in blood glucose, plasma insulin and triacylglycerol levels as well as the reduction in insulin sensitivity caused by dexamethasone treatment was not exacerbated in the VCD+DEX group of rats. Premature ovarian failure did change neither the hepatic content of glycogen and triacylglycerol nor the glycerol release from perigonadal adipose tissue. Glucose intolerance was observed in the VCD group after an ipGTT (p<0.05), but not after an oral glucose challenge. Glucose intolerance and compensatory pancreatic β-cell mass caused by GC were not modified by ovarian failure in the VCD+DEX group. We conclude that reduced ovarian function has no major implications on the diabetogenic effects promoted by GC treatment, indicating that other factors related to aging may make rats more vulnerable to GC side effects on glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment

Battiston

Santos

Barbosa

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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“…The adverse effects of GCs on glucose homeostasis are well known in human subjects (Beard et al 1984;Willi et al 2002;Nicod et al 2003) and have been well reproduced in rodent models subjected to GC treatment (Stojanovska et al 1990;Novelli et al 1999;Rafacho et al 2010Rafacho et al , 2011. The side effects of GC on rat glucose homeostasis may include increased blood glucose levels, glucose intolerance, reduction of insulin sensitivity and (or) glucose clearance, and the presence of hyperinsulinemia (for a review see Rafacho et al 2012). When GC is administered under specific conditions, e.g., to obese rats (Ohneda et al 1993) or rats prone to develop diabetes (Ogawa et al 1992), it may aggravate an already disrupted glucose metabolism and lead to the development of overt hyperglycemia.…”

Section: Introductionmentioning

confidence: 97%

Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats

Santos

Ferreira

Gonçalves-Neto

et al. 2014

Can. J. Physiol. Pharmacol.

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The disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The β-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats.

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“…GC actions vary in a tissue-and cell-specific manner, and depend on the dosage, length of administration (acute or chronic), source (endogenous or synthetic), the species investigated (e.g., human, rodents), individual susceptibility (e.g., insulin-resistant, glucose-intolerant), among other questions (e.g., direct vs. indirect actions) that make difficult to obtain a general consensus about their actions [7] .…”

Section: Research Highlightmentioning

confidence: 99%

“…Dexamethasone and prednisone/prednisolone show potent immunosuppressive, anti-inflammatory and antiallergic effects, which justify their wide prescription for the treatment of chronic autoimmune diseases, inflammatory diseases, organ transplant rejection, among others [6] . However, chronic exposure to the GCs impairs the normal metabolic homeostasis and causes deleterious adverse effects as demonstrated clinically and experimentally including hyperglycemia, glucose intolerance, dyslipidemia, peripheral insulin resistance, muscle wasting, hepatosteatosis, infertility, growth retardation, cognitive dysfunction, glaucoma, cataracts, topical skin thinning, osteoporosis and diabetes, among others [6][7][8] .…”

Section: Research Highlightmentioning

confidence: 99%

How much we know about the attenuation of insulin signaling in the adipose tissue caused by glucocorticoid treatment?

Rafacho

Nunes²,

Bordin³

2015

Inflamm Cell Signal

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Glucocorticoid (GC) hormone exerts numerous physiological roles that include modulation of immune, nervous, cardiovascular and metabolic systems. Synthetic GCs such as dexamethasone and prednisone/prednisolone are widely prescribed in the clinical context to the treatment of inflammatory-related diseases. In spite of its positive therapeutic effect, GC-based therapies may cause several adverse effects including glucose intolerance and peripheral insulin resistance. Reduction of insulin sensitivity in the adipocytes and adipose tissue caused by GC treatment is associated with increased lipolysis and abnormal Ser phosphorylation of insulin substrate receptor (IRS)-1 and protein kinase B (PKB). However, there is no consensus about the precise mechanisms whereby GC treatment promotes such attenuation in the insulin signaling pathway. In this paper, we will briefly discuss and present some molecular evidences that might be involved with this negative impact of GC in the insulin signaling in the adipose tissue.

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Functional and Molecular Aspects of Glucocorticoids in the Endocrine Pancreas and Glucose Homeostasis

Cited by 6 publications

References 103 publications

Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment

Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment

Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats

How much we know about the attenuation of insulin signaling in the adipose tissue caused by glucocorticoid treatment?

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