The Effect of Hypoxia on Plasma Leptin and Insulin in Newborn and Juvenile Rats

Raff, Hershel; Bruder, Eric D.; Jankowski, Barbara M.

doi:10.1385/endo:11:1:37

Cited by 51 publications

(44 citation statements)

References 15 publications

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“…The findings of growth retardation and increased adiponectin in this study, and insulin resistance in previous experiments using the same treatment paradigm ( 7,9,12 ), are similar to a variety of other pathophysiological states including prenatal growth restriction ( 25 ) and anorexia or bulimia nervosa ( 26,27 ). This "paradoxical" increase in adiponectin may be a response to, rather than a cause of, changes in insulin resistance.…”

Section: Discussionsupporting

confidence: 85%

“…It is possible that the marked increases in adiponectin in the current study were in response to the decrease in insulin sensitivity we have previously demonstrated ( 7,9,12 ).…”

Section: Discussionmentioning

confidence: 68%

“…We have extensively characterized the short-term endocrine and metabolic effects of hypoxia from birth to 7 d of age. Briefly, hypoxia from birth induces a decrease in weight gain without a significant change in body composition ( 7,8 ) and a state of relative insulin resistance ( 7,9,10 ). Furthermore, we have recently demonstrated that a tapering regimen of the glucocorticoid dexamethasone, administered to mimic clinical practice ( 11 ), results in hyperinsulinemia with normoglycemia and decreased weight gain ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Raff

Bruder

2006

ENDO

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Hypoxia is a common neonatal stress that induces insulin resistance and a decrease in body weight gain. Dexamethasone is often used to treat neonatal cardiopulmonary disease, and also leads to insulin resistance and a decrease in body weight gain. The current study addressed the hypothesis that serum concentrations of the adipokines adiponectin and/or resistin are altered during hypoxia and/or dexamethasone therapy in neonatal rats. Rat pups with their lactating dams were exposed to hypoxia (11% O 2 ) from birth and treated with a tapering regimen of dexamethasone from postnatal day (PD) 3-6. Serum adiponectin and resistin were measured on PD7. Hypoxia and dexamethasone independently decreased body weight gain and increased adiponectin levels. The combination of hypoxia and dexamethasone did not further increase adiponectin. Dexamethasone caused a small increase in resistin in normoxic pups, which may facilitate the hyperinsulemic-normoglycemic state we previously described. We also conclude that adiponectin is increased during hypoxia in response to a decrease in the sensitivity to insulin.

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Section: Discussionsupporting

confidence: 85%

“…It is possible that the marked increases in adiponectin in the current study were in response to the decrease in insulin sensitivity we have previously demonstrated ( 7,9,12 ).…”

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Raff

Bruder

2006

ENDO

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“…Our data do suggest that some factor(s) other than ACTH may be causing the increased corticosteronogenesis and adrenal weight in hypoxic pups. Because increased leptin has been shown to inhibit corticosterone but not aldosterone production in adult rats (20), it is possible that a decrease in leptin that we have demonstrated in hypoxic rat pups (24,25) allowed an increased steroidogenic response in the ZF/R but not the ZG.…”

Section: Discussionmentioning

confidence: 85%

“…Although these beneficial effects are numerous, several are worth special mention. One effect we have demonstrated involving increased corticosterone is a significant decrease in insulin sensitivity (24,25). This is likely to maintain glucose delivery to the brain and heart under hypoxic conditions.…”

Section: Perspectivesmentioning

confidence: 78%

Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR

Raff

Hong

Oaks

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 Ϯ 1.4 ng/ml; n ϭ 12) and ACTHstimulated (94.0 Ϯ 9.4 ng/ml; n ϭ 14) corticosterone levels compared with normoxic controls (basal ϭ 8.3 Ϯ 0.5 ng/ml; n ϭ 11; stimulated ϭ 51.3 Ϯ 3.8 ng/ml; n ϭ 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 Ϯ 4 vs. 78 Ϯ 8 pg/ml) or after (481 Ϯ 73 vs. 498 Ϯ 52 pg/ml) porcine ACTH injection (20 g/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1␣ mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate. adrenocorticotropin; aldosterone; newborn; steroidogenic acute regulatory protein; peripheral-type benzodiazepine receptor; hypoxia-inducible factor HYPOXIA is one of the most common causes of neonatal morbidity and mortality (10, 17). Considerable attention has been paid to the short-and long-term neurological, cardiopulmonary, and renal consequences of neonatal hypoxia (3,8,14,34,36). In comparison, the adrenal adaptation in vivo to prolonged neonatal hypoxia has not been extensively studied. One pertinent study in human infants with hypoxemia due to bronchiolitis demonstrated an augmented cortisol, but not aldosterone, response to ACTH (12). This suggests a zone-specific adrenal adaptation to hypoxia.We have extensively examined dispersed adrenal cells in vitro removed from suckling rats exposed to hypoxia from birth (28). We have found that, as opposed to adult rats (29), steroidogenesis in vitro is augmented in adrenal cells from hypoxic neonatal rats despite no changes in steroidogenic enzy...

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Neonatal Hypoxia in the Rat: Effects on Exocrine Pancreatic Development

Lee,

Struve,

Lewis

et al. 2002

J. pediatr. gastroenterol. nutr.

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BackgroundGlucocorticoids profoundly affect pancreatic development during the suckling period. Increases in circulating glucocorticoids during exposure to hypoxia may alter the normal pattern of pancreatic enzyme development.MethodsRats were exposed to hypoxia from birth to 7 days (suckling) or from 28 to 35 days of age (weaned at day 21).ResultsHypoxia in neonatal rats (0–7 days) led to decreased pancreatic weight, and trypsin, lipase, and amylase activity compared with normoxic controls. In contrast, rats exposed to hypoxia from 28 to 35 days of age had decreased lipase activity but no change in other pancreatic parameters. Two weeks after hypoxia (0–7 days) pups were returned to normoxia, and their body weights remained smaller than the age‐matched, previously normoxic controls. Pancreatic enzyme activities were decreased in the group recovering from hypoxia compared with controls. Recovery of enzyme activities was observed 3 weeks after hypoxic rats were returned to normoxia. Normoxic pups were given dexamethasone to simulate the hyperglucocorticoid state in hypoxia at 7‐day olds. Dexamethasone administration led to decreased body weight, but increased pancreatic weight and enzyme activity compared with normoxic, age‐matched controls.ConclusionsHypoxia in newborn rats delays the maturation of pancreatic exocrine enzymes. The mechanism is not related to increased serum glucocorticoids.

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The Effect of Hypoxia on Plasma Leptin and Insulin in Newborn and Juvenile Rats

Cited by 51 publications

References 15 publications

Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR

Neonatal Hypoxia in the Rat: Effects on Exocrine Pancreatic Development

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