Physiological roles of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase

White, Perrin C.; Rogoff, Daniela; McMillan, D. Randy

doi:10.1097/mop.0b013e328305e439

Cited by 15 publications

(8 citation statements)

References 33 publications

(31 reference statements)

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“…HSD11B1 (hydroxysteroid 11-beta-dehydrogenase 1) converts inactive cortisone into its active form cortisol, whereas the other isoform HSD11B2 catalyzes the back reaction. The enzyme HSD11B1 may play a role in adipose tissue development due to its increased mRNA levels and activity in most obese humans (White et al, 2008). The interplay between E2 and HSD11B1 was also studied by Engeli et al evaluating the expression of different HSD11B isoforms in adipose tissue of aged women.…”

Section: E2 In Adipose Tissue and Agingmentioning

confidence: 99%

Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

Wend¹,

Wend²,

Krum³

2012

Front. Endocrin.

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The roles of estrogens have been best studied in the breast, breast cancers, and in the female reproductive tract. However, estrogens have important functions in almost every tissue in the body. Recent clinical trials such as the Women’s Health Initiative have highlighted both the importance of estrogens and how little we know about the molecular mechanism of estrogens in these other tissues. In this review, we illustrate the diverse functions of estrogens in the bone, adipose tissue, skin, hair, brain, skeletal muscle and cardiovascular system, and how the loss of estrogens during aging affects these tissues. Early transcriptional targets of estrogen are reviewed in each tissue. We also describe the tissue-specific effects of selective estrogen receptor modulators (SERMs) used for the treatment of breast cancers and postmenopausal symptoms.

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Section: E2 In Adipose Tissue and Agingmentioning

confidence: 99%

Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

Wend¹,

Wend²,

Krum³

2012

Front. Endocrin.

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“…23 H6PDH-deficient mice are not reported to have neutrophil abnormalities. 24,25 In contrast, G6Pase-␤-deficient mice do manifest neutrophil dysfunction 10 that mimic those in GSD-Ib patients. 1,9 This suggests that G6Pase-␤ provides the primary pathway of glucose metabolism in the ER and represents an additional G6P-utilization pathway that regulates neutrophil function.…”

Section: Introductionmentioning

confidence: 99%

Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

Jun

Lee

Cheung

et al. 2010

Blood

137

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G6PC3 deficiency, characterized by neutropenia and neutrophil dysfunction, is caused by deficiencies in the endoplasmic reticulum (ER) enzyme glucose-6-phosphatase-␤ (G6Pase-␤ or G6PC3) that converts glucose-6-phosphate (G6P) into glucose, the primary energy source of neutrophils. Enhanced neutrophil ER stress and apoptosis underlie neutropenia in G6PC3 deficiency, but the exact functional role of G6Pase-␤ in neutrophils remains unknown. We hypothesized that the ER recycles G6Pase-␤-generated glucose to the cytoplasm, thus regulating the amount of available cytoplasmic glucose/ G6P in neutrophils. Accordingly, a G6Pase-␤ deficiency would impair glycolysis and hexose monophosphate shunt activities leading to reductions in lactate production, adenosine-5-triphosphate (ATP) production, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Using annexin V-depleted neutrophils, we show that glucose transporter-1 translocation is impaired in neutrophils from G6pc3 ؊/؊ mice and G6PC3-deficient patients along with impaired glucose uptake in G6pc3 ؊/؊ neutrophils. Moreover, levels of G6P, lactate, and ATP are markedly lower in murine and human G6PC3-deficient neutrophils, compared with their respective controls. In parallel, the expression of NADPH oxidase subunits and membrane translocation of p47 phox are down-regulated in murine and human G6PC3-deficient neutrophils. The results establish that in nonapoptotic neutrophils, G6Pase-␤ is essential for normal energy homeostasis. A G6Pase-␤ deficiency prevents recycling of ER glucose to the cytoplasm, leading to neutrophil dysfunction. (Blood. 2010;116(15):2783-2792) IntroductionThere are 2 enzymatically active glucose-6-phosphatases (G6Pases), the liver/kidney/intestine-restricted G6Pase-␣ (or G6PC) 1,2 and the ubiquitously expressed G6Pase-␤ (also known as G6PC3). 3,4 Both enzymes are transmembrane endoplasmic reticulum (ER) proteins, with a similar topology, that places their active site on the luminal side of the ER membrane. 5,6 Both have similar kinetic properties 2,4 and hydrolyze glucose-6-phosphate (G6P) to glucose and phosphate when coupled with the ubiquitously expressed G6P transporter (G6PT) that translocates G6P from the cytoplasm into the lumen of the ER. 7,8 The primary role of the G6Pase/G6PT complex is to provide glucose and phosphate to the ER lumen. The G6Pase-␣/G6PT complex maintains blood glucose homeostasis between meals by hydrolyzing G6P to glucose in the terminal step of gluconeogenesis and glycogenolysis. 1,2 Deficiencies in G6Pase-␣ cause glycogen storage disease type Ia (GSD-Ia) and deficiencies in G6PT result in GSD type Ib (GSD-Ib). 1,2,9 Both GSD-Ia and GSD-Ib patients manifest a phenotype of disturbed blood glucose homeostasis with GSD-Ib patients also suffering neutropenia and neutrophil dysfunction, 1,9 reflecting a role of G6PT in tissues beyond the liver and kidney.The biologic roles of G6Pase-␤ and the G6Pase-␤/G6PT complex are poorly defined. Neutrophils, which express both G6Pase-␤ and G6PT, 10 are capable ...

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“…The 11βHSD1, an endoplasmic reticulum-bound enzyme, is typically expressed in glucocorticoid receptor-rich tissues (e.g. liver, brain, lung, and adipose tissue) and is responsible for the conversion of inactive cortisone to an active cortisol (56). The 11βHSD1 plays a key role in the development of metabolic syndrome and Cushing's syndrome (57,58) and 11βHSD1 knockout mice are resistant to the development of metabolic syndrome (59).…”

Section: Discussionmentioning

confidence: 99%

Possible mechanisms of the hypoglycaemic effect of artesunate: Gender implication

Alagbonsi

Salman

Sulaiman

et al. 2020

Preprint

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Background Artesunate is an antimalarial drug that affects glucose homeostasis but the mechanism of its glucose-modulating effect is not fully understood especially with gender implication, which is the information this study sought to provide. Methods Twenty-five (25) male and 25 female rats were separately and blindly allocated into five identical groups (n = 5/group). Group I (control) received 0.2 ml/kg distilled water. Groups II and III both received 2.90 mg/kg artesunate on day one, but 1.45 mg/kg from day two till day five and day fifteen respectively. Groups IV and V both received 8.70 mg/kg artesunate on day one, but 4.35 mg/kg artesunate from day two till day five and day fifteen respectively. Results In male rats, the blood glucose was reduced by low and high doses of artesunate at 5 days but increased by high dose at 15 days. Glucose was reduced in female rats but unchanged in male rats by low dose artesunate at 15 days. Artesunate increased glycogen concentration at short duration which normalised at long duration in both genders. Artesunate increased G6P concentration only in male rats at 15 days but reduced G6Pase activity in male and female rats (except in those that received low and high doses of artesunate for 15 days). Artesunate increased insulin only in male rats treated with low dose artesunate for 5 days. Artesunate increased cortisol concentration in male but reduced it in female rats. Artesunate decreased glucagon concentration except in female rats treated with high dose for 5 days. Artesunate increased oestrogen concentration in male rats that received low dose artesunate for 5 days but reduced it in female rats that received high dose for 15 days. Except in male rats that received high dose of artesunate for 15 days where testosterone was increased, artesunate did not affect testosterone concentration in all other male and female groups Conclusions The present study suggests that artesunate causes reduction in plasma glucose by reducing plasma glucagon concentrations and inhibiting liver glycogenolysis via inhibition of G6Pase activity in both sexes. In addition, increase in plasma insulin concentration contributed to the reduction in blood glucose caused by artesunate in male but not female rats; and artesunate-induced increase in G6P, a substrate for G6PD, could enhance NADPH generation and antioxidant enzyme activation in male rats.

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Physiological roles of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase

Abstract: Hexose-6-phosphate dehydrogenase and 11 beta-hydroxysteroid dehydrogenase type 1 may play important roles in the pathogenesis of obesity and metabolic syndrome. Although the importance of polymorphisms in the corresponding genes remains uncertain, rare mutations have not been ruled out.

Cited by 15 publications

References 33 publications

Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

Lack of glucose recycling between endoplasmic reticulum and cytoplasm underlies cellular dysfunction in glucose-6-phosphatase-β–deficient neutrophils in a congenital neutropenia syndrome

Possible mechanisms of the hypoglycaemic effect of artesunate: Gender implication

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