Chronic Prednisolone Treatment Reduces Hepatic Insulin Sensitivity while Perturbing the Fed-to-Fasting Transition in Mice

Laskewitz, Anke; Dijk, Theo H. van; Bloks, Vincent W.; Reijngoud, Dirk-Jan; Lierop, Marie-José van; Dokter, Wim H.A.; Kuipers, Folkert; Groen, Albert K.; Grefhorst, Aldo

doi:10.1210/jcem.95.3.9991

Cited by 2 publications

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“…In an earlier study (18), we showed that, under chow-fed conditions, sustained treatment of C57BL/6J mice with prednisolone reduced insulin sensitivity only in a very subtle manner under fasting conditions. In this subsequent study, we show that in mice challenged with a high-fat diet, prednisolone treatment did not aggravate insulin resistance induced by a high-fat diet as measured by HIEC, even though these mice appeared insulin resistant because HOMA-IR was increased and whole-body glucose kinetics at basal prevailing insulin concentrations were perturbed.…”

Section: Discussionmentioning

confidence: 83%

“…Plasma insulin, corticosterone, and fibroblast growth factor-21 (FGF21) concentrations were measured using commercially available ELISA kits (Mercodia ultrasensitive mouse insulin ELISA; Orange Medical, Tilburg, The Netherlands; Diagnostic System Laboratories Benelux, Assendelft, The Netherlands; and Millipore, Amsterdam, The Netherlands, respectively). The homeostatic assessment model of insulin resistance (HOMA-IR) was calculated adjusted for basal mouse values taken from a chow-fed vehicle-treated group as previously described (18). Plasma nonesterified (or free) fatty acid (NEFA) and 3-hydroxybutyrate concentrations were determined with commercially available kits (Diasys, Holzheim, Germany, and Wako Chemicals, Neuss, Germany, respectively).…”

Section: Metabolite Analysismentioning

confidence: 99%

“…RNA was isolated from liver and white adipose tissue, and gene expression was measured as previously described (18). The sequence of the primers and probes that were previously used can be found on http://www.labpediatricsrug.nl and are deposited at RTPrimerDB (http://www.rtprimerdb.org).…”

Section: Gene Expression Analysismentioning

confidence: 99%

“…We have recently shown that chronic prednisolone treatment for 7 d in C57BL/6J mice kept on a standard laboratory chow does affect hepatic glucose production (HGP) in the fasted state in a very subtle manner (18). When the gold standard to determine insulin sensitivity, i.e.…”

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confidence: 99%

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Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

Laskewitz¹,

Dijk

Grefhorst³

et al. 2012

Endocrinology

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Synthetic glucocorticoids such as prednisolone have potent antiinflammatory actions. Unfortunately, these drugs induce severe adverse effects in patients, many of which resemble features of the metabolic syndrome, such as insulin resistance. In this study, we investigated whether adverse effects of prednisolone on glucose homeostasis are aggravated in mice with compromised insulin sensitivity due to a high-fat diet by applying various methods to analyze changes in insulin sensitivity in mice. C57BL/6J mice were fed a high-fat diet for 6 wk and treated with either prednisolone (10 mg/kg · d) or vehicle for the last 7 d. Insulin sensitivity and blood glucose kinetics were analyzed with state-of-the-art stable isotope procedures in different experimental conditions. Prednisolone treatment aggravated fasting hyperglycemia and hyperinsulinemia caused by high-fat feeding, resulting in a higher homeostatic assessment model of insulin resistance. In addition, prednisolone-treated high-fat diet-fed mice appeared less insulin sensitive by detailed analysis of basal glucose kinetics. Remarkably, using hyperinsulinemic-euglycemic or hyperglycemic clamp techniques, neither hepatic nor peripheral insulin resistance was worsened in the group that was treated with prednisolone. Yet analysis of hepatic glucose metabolism revealed that prednisolone did alter glycogen balance by reducing glycogen synthase flux under hyperinsulinemic as well as hyperglycemic conditions. In addition to elevated insulin levels, prednisolone-treated mice showed a major rise in plasma leptin and fibroblast growth factor 21 levels. Our data indicate that prednisolone-induced adverse effects on glucose metabolism in high-fat diet-fed mice do not reflect impaired insulin sensitivity but may be caused by other changes in the hormonal regulatory network controlling glucose metabolism such as fibroblast growth factor 21 and leptin.

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Section: Discussionmentioning

confidence: 83%

Section: Metabolite Analysismentioning

confidence: 99%

Section: Gene Expression Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

Laskewitz¹,

Dijk

Grefhorst³

et al. 2012

Endocrinology

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“…Disruptions in stress reactivity, specifically increased exposure to cortisol, have been implicated in total and abdominal obesity, metabolic syndrome, and insulin resistance (7)(8)(9)(10). Furthermore, models of chronic exposure to elevated cortisol, such as in Cushing's Syndrome and animal models of exogenous cortisol treatment or increased stress, have directly shown that cortisol exposure leads to abdominal obesity and cardiometabolic disease (11)(12)(13)(14). Whereas these models of chronic exposure provide evidence for the causal role of cortisol in obesity and its related co-morbidities, the level of cortisol exposure in these models are substantially elevated beyond that experienced by humans in normal daily living.…”

Section: Introductionmentioning

confidence: 99%

Modifying influence of dietary sugar in the relationship between cortisol and visceral adipose tissue in minority youth

Gyllenhammer

Weigensberg

Spruijt‐Metz

et al. 2013

Obesity

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Objective Cortisol has been associated with preferential visceral adipose tissue (VAT) deposition; however findings in humans are mixed, which may be clarified when diet is considered. Design and Methods Participants included 165 African American and Latino, overweight adolescents (BMI% 97.2±3.2%, ages 13-18, 67% Latino, 66% female). Body composition was determined by DEXA, abdominal fat depots (VAT, subcutaneous (SAT)) by multiple-slice MRI, time-controlled serum sample to measure cortisol, and 2-day multi-pass 24-hour dietary recall. Linear regression analysis examined the cross-sectional relationship between cortisol, and the interaction of diet and cortisol on adiposity measures. Sex, race, age and total body fat were a priori covariates. Results There was a significant interaction between cortisol and sugar (total and added) in the prediction of VAT (pinteraction<=0.05). Amongst participants with high total or added-sugar intake, cortisol was significantly associated with VAT (β=0.031 p<0.001; β=0.026 p<0.001), with no relationship in low consumers of total or added-sugar. Conclusion Dietary sugar may play an important role in modifying the relationship between cortisol and VAT, such that cortisol is significantly associated with elevated VAT under conditions of high sugar intake.

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Chronic Prednisolone Treatment Reduces Hepatic Insulin Sensitivity while Perturbing the Fed-to-Fasting Transition in Mice

Cited by 2 publications

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Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

Modifying influence of dietary sugar in the relationship between cortisol and visceral adipose tissue in minority youth

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