Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase.

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Abstract Text:

Daniela Rogoff,Jeffrey W Ryder,Kelli Black,Zheng Yan,Shawn C Burgess,D Randy McMillan,Perrin C White,

Hexose-6-phosphate dehydrogenase (EC 1.1.1.47) catalyzes the conversion of glucose 6-phosphate to 6-phosphogluconolactone within the lumen of the endoplasmic reticulum, thereby generating reduced nicotinamide adenine dinucleotide phosphate. Reduced nicotinamide adenine dinucleotide phosphate is a necessary cofactor for the reductase activity of 11beta-hydroxysteroid dehydrogenase type 1 (EC 1.1.1.146), which converts hormonally inactive cortisone to active cortisol (in rodents, 11-dehydrocorticosterone to corticosterone). Mice with targeted inactivation of hexose-6-phosphate dehydrogenase lack 11beta-hydroxysteroid dehydrogenase type 1 reductase activity, whereas dehydrogenase activity (corticosterone to 11-dehydrocorticosterone) is increased. We now report that both glucose output and glucose use are abnormal in these mice. Mutant mice have fasting hypoglycemia. In mutant primary hepatocytes, glucose output does not increase normally in response to glucagon. Mutant animals have lower hepatic glycogen content when fed and cannot mobilize it normally when fasting. As assessed by RT-PCR, responses of hepatic enzymes to fasting are blunted; enzymes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase, tyrosine aminotransferase) are not appropriately up-regulated, and expression of glucokinase, an enzyme required for glycolysis, is not suppressed. Corticosterone has attenuated effects on expression of these enzymes in cultured mutant primary hepatocytes. Mutant mice have increased sensitivity to insulin, as assessed by homeostatic model assessment values and by increased glucose uptake by the muscle. The hypothalamic-pituitary-adrenal axis is also abnormal. Circulating ACTH, deoxycorticosterone, and corticosterone levels are increased in mutant animals, suggesting decreased negative feedback on the hypothalamic-pituitary-adrenal axis. Comparison with other animal models of adrenal insufficiency suggests that many of the observed abnormalities can be explained by blunted intracellular corticosterone actions, despite elevated circulating levels of this hormone.

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Publishing Authors By Initials

D Rogoff,JW Ryder,K Black,Z Yan,SC Burgess,DR McMillan,PC White,

For similar endocrine system: endocrine glands: pituitary-adrenal system research abstracts see: endocrine system: endocrine glands: pituitary-adrenal system research

PUBMED ID PMID:

MEDLINE DATE:

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Endocrinology

VOLUME: 148

Page Numbers: 5072-80

Journal Abbreviation: Endocrinology

ISSN: 0013-7227

DAY: 26

MONTH: 07

YEAR: 2007

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 375040

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Keywords Mesh Terms:

KEYWORDS: Pituitary-Adrenal System

MESH TERMS: metabolism

Chemical & Substance for Abstract: Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase. Information

Substance Name: galactose-6-phosphate dehydrogenase

Registry Number: EC 1.1.1.-

Grant and Affiliation Information for Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase.

AFFILIATION: University of Texas Southwestern Medical Center, 5223 Harry Hines Boulevard, Dallas, TX 75390-9063, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: U24 DK 076169

ACRONYM: DK

MEDLINETA: Endocrinology

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Abnormalities of glucose homeostasis and the hypothalamic-pituitary-adrenal axis in mice lacking hexose-6-phosphate dehydrogenase Related Publications

• A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility.
• A voltage-sensor water pore.
• Chronic vague abdominal pain in children.
• Cimetidine use and the risk for prostate cancer: results from the VITAL cohort study.
• Do breast cancer risk factors modify the association between hormone therapy and mammographic breast density? (United States).
• Effects of photoperiod and intermittent lighting on reproduction in pheasant hens.
• Exposure to the metabolic inhibitor sodium azide induces stress protein expression and thermotolerance in the nematode Caenorhabditis elegans.
• Extremity trauma research in the United States army.
• Felbamate is a subunit selective modulator of recombinant gamma-aminobutyric acid type A receptors expressed in Xenopus oocytes.
• Harnessing RNAi for Analyses of Ras Signaling and Transformation.
• In vitro maturation and fertilization of swamp buffalo oocytes and their subsequent development.
• Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen.
• Inhibitory control in children with phenylketonuria.
• Kinetic mechanism of myosinV-S1 using a new fluorescent ATP analogue.
• Mammographic breast density, dense area, and breast area differences by phase in the menstrual cycle.
• PGI2 opens potassium channels in retinal pericytes by cyclic AMP-stimulated, cross-activation of PKG.
• Parachutes and prophylaxis: they both work!
• Polyol synthesis through hydrocarbon oxidation: de novo synthesis of L-galactose.
• Post-thawing survival of motile ram sperm after isolation by layering on protein columns.
• Prevalence of Borrelia burgdorferi in small mammals in New York state.
• Prospects for sexing mammalian sperm edited by Rupert P. Amman and George E. Seidel, Jr.; 288 pages; Cloth - $32.50, Paper - $22.50. Available from Colorado Associated University Press, 1338 Grandview Avenue, Box 480, University of Colorado, Boulder, Colo
• Ras-Sensitive IMP Modulation of the Raf/MEK/ERK Cascade Through KSR1.
• Relationship between estrone sulfate in plasma and litter size at farrowing for sows and gilts.
• Spontaneous baroreflex sensitivity in young and older people during voluntary and electrically evoked isometric exercise.
• Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation.
• The impact of aryl hydrocarbon receptor signaling on matrix metabolism: implications for development and disease.
• The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria.
• The preference of tryptophan for membrane interfaces.
• The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling.
• Using verbal fluency to detect very mild dementia of the Alzheimer type.