Glycyrrhizic acid is a component of licorice. It can cause hypokalemia through the inhibition of 11beta-hydroxysteroid dehydrogenase. The severity of symptoms depends on the dose and duration of licorice intake, as well as the individual susceptibility. The safe dose of licorice is 10 mg per day. Even a small amount of licorice can cause side effects, including hypokalemia in patients taking diuretics, with diarrhea, or congestive heart failure. We experienced a 59-year-old male with muscle weakness. He had ingested losartan and indapamide due to hypertension. At presentation, he had ingested 8 mg of licorice daily for the previous 17 days. The patient presented with severe hypokalemia (1.8 mEq/L) and rhabdomyolysis. His renin activity was 0.44 ng/mL/h, and his aldosterone level was 6.0 pg/mL. After cessation of licorice and indapamide, his potassium level recovered. In conclusion, even a small amount of licorice can induce hypokalemia in patients who are taking diuretics.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Diarrhea ; Diuretics ; Glycyrrhiza ; Glycyrrhizic Acid ; Heart Failure ; Humans ; Hypertension ; Hypokalemia ; Indapamide ; Losartan ; Male ; Middle Aged ; Muscle Weakness ; Potassium ; Renin ; Rhabdomyolysis

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.
11-beta-Hydroxysteroid Dehydrogenases ; Adipocytes ; Adipocytes, White ; Adipokines ; Adiponectin ; Adipose Tissue ; Anoxia ; Cardiovascular Diseases ; Homeostasis ; Inflammation ; Insulin Resistance ; Metabolism ; Mitochondria ; Nitric Oxide ; Obesity ; Quality Control

Nephrotic syndrome and liver cirrhosis are common clinical manifestations, and are associated with avid sodium retention leading to the development of edema and ascites. However, the mechanism for the sodium retention is still incompletely understood and the molecular basis remains undefined. We examined the changes of sodium (co)transporters and epithelial sodium channels (ENaCs) in the kidneys of experimental nephrotic syndrome and liver cirrhosis. The results demonstrated that puromycin- or HgCl2?induced nephrotic syndrome was associated with 1) sodium retention, decreased urinary sodium excretion, development of ascites, and increased plasma aldosterone level; 2) increased apical targeting of ENaC subunits in connecting tubule and collecting duct segments; and 3) decreased protein abundance of type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2). Experimental liver cirrhosis was induced in rats by CCl4 treatment or common bile duct ligation. An increased apical targeting of alpha-, beta-, and gamma-ENaC subunits in connecting tubule, and cortical and medullary collecting duct segments in sodium retaining phase of liver cirhosis but not in escape phase of sodium retention. Immunolabeling intensity of 11betaHSD2 in the connecting tubule and cortical collecting duct was significantly reduced in sodium retaining phase of liver cirrhosis, and this was confirmed by immunoblotting. These observations therefore strongly support the view that the renal sodium retention associated with nephrotic syndrome and liver cirrhosis is caused by increased sodium reabsorption in the aldosterone sensitive distal nephron including the connecting tubule and collecting duct, and increased apical targeting of ENaC subunits plays a role in the development of sodium retention in nephrotic syndrome and liver cirrhosis.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Animals* ; Ascites ; Common Bile Duct ; Edema ; Epithelial Sodium Channels ; Immunoblotting ; Kidney ; Ligation ; Liver Cirrhosis* ; Liver Cirrhosis, Experimental ; Liver* ; Models, Animal* ; Nephrons ; Nephrotic Syndrome* ; Plasma ; Rats ; Sodium ; United Nations

This paper was designed to observe the colocalization of 11beta-HSD1 and GR, and its significance in the rat hippocampus. Immunocytochemical dual-staining showed that not only 11beta-HSD1 but also GR immunoreactive substances were present in the cultured rat hippocampal neurons. Moreover, they were colocalized in the same hippocampal neuron. Synthetic glucocorticoid dexamethasone (DEX) up-regulated the protein expression and activity of 11beta-HSD1 in the cultured hippocampal neurons, as determined by Western blot and thin layer chromatography (TLC) respectively. The transfection of PC12 cells with the plasmid containing promoter sequence of 11beta-HSD1 gene and the reporter gene of CAT enzyme was conducted. DEX up-regulated the reporter gene expression in the system described above. The up-regulation of 11beta-HSD1 and reporter gene expression induced by DEX were both blocked by GR antagonist RU38486. Our study suggests that the colocalization of 11beta-HSD1 and GR in the hippocampus may be implicated in the up-regulation of 11beta-HSD1 expression by glucocorticoids combining to its promoter region, which in turn produces more biologically active glucocorticoids necessary for the binding of low affinity of GR.
11-beta-Hydroxysteroid Dehydrogenases ; genetics ; metabolism ; Animals ; Animals, Newborn ; Dexamethasone ; pharmacology ; Gene Expression Regulation ; Hippocampus ; cytology ; metabolism ; Mifepristone ; pharmacology ; Neurons ; chemistry ; metabolism ; PC12 Cells ; Promoter Regions, Genetic ; Rats ; Receptors, Glucocorticoid ; genetics ; metabolism ; Transfection

A high intake of licorice can cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure and depression of renin-angiotensin-aldosterone system. Glycyrrhizic acid, a component of licorice, produces hypermineralocorticoidism through the inhibition of 11beta-hydroxysteroid dehydrogenase. We report a 55-year-old woman with severe muscle weakness with hypokalemia(Serum K+ : 1.7 mEq/ L) due to raw licorice tea. She boiled the licorice 50 g in water and drunk intermittently for 4 months due to her foreign body sensation on her throat. In Korea there is a traditional recipe that licorice works out for the above symptom. Her serum renin activity and aldosterone level were far beyond normal range which was typical to licorice ingestion. She also had metabolic alkalosis with pH 7.55 and hypertension. After quitting the licorice, hypokalemia and muscle weakness gradually improved and her blood pressure returned to normal.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Alkalosis ; Blood Pressure ; Depression ; Eating ; Edema ; Female ; Foreign Bodies ; Glycyrrhiza* ; Glycyrrhizic Acid ; Humans ; Hydrogen-Ion Concentration ; Hypertension ; Hypokalemia* ; Korea ; Middle Aged ; Muscle Weakness ; Pharynx ; Potassium ; Reference Values ; Renin ; Renin-Angiotensin System ; Sensation ; Sodium ; Tea ; Water

The present study was aimed at investigating the role of type II 11beta-hydroxysteroid dehydrogenase (IIbeta- HSD II) in the development of hypertension. Two-kidney, one-clip (2K1C), deoxycorticosterone acetate (DOCA)/salt, or NG-nitro-L-arginine methyl ester (L-NAME) hypertension was induced in male Sprague- Dawley rats. Four weeks later, the expression of 11beta-HSD II mRNA was determined in the kidney by Northern blot analysis. The plasma level of aldosterone was measured by radioimmunoassay. In 2K1C hypertension, the expression of 11beta-HSD II was decreased in the clipped kidney and increased in the non-clipped kidney. The expression was increased in the remnant kidney of DOCA/salt hypertension, while decreased in the kidneys of L-NAME hypertension. The plasma level of aldosterone was increased, decreased, and remained unchanged in 2K1C, DOCA/salt, and L-NAME hypertension, respectively. The down-regulation of 11beta-HSD II may contribute to the sodium retention, thereby increasing the blood pressure in 2K1C and L-NAME hypertension. On the contrary, the up-regulation in DOCA/salt hypertension may play a compensatory role to dissipate the sodium retention.
11-beta-Hydroxysteroid Dehydrogenases* ; Aldosterone ; Animals ; Blood Pressure ; Blotting, Northern ; Desoxycorticosterone ; Down-Regulation ; Humans ; Hypertension* ; Kidney* ; Male ; NG-Nitroarginine Methyl Ester ; Plasma ; Radioimmunoassay ; Rats* ; RNA, Messenger ; Sodium ; Up-Regulation

The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11beta-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding, effective treatment for hypothalamic obesity has not yet been developed. Therefore, understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology, endocrine characteristics, and treatment strategies of hypothalamic obesity.
11-beta-Hydroxysteroid Dehydrogenases ; Adipose Tissue ; Adolescent* ; Body Weight ; Child* ; Eating ; Energy Metabolism ; Homeostasis ; Humans ; Hypothalamus ; Insulin ; Leptin ; Melatonin ; Obesity* ; Obesity, Morbid ; Prader-Willi Syndrome ; Pro-Opiomelanocortin ; Radiotherapy ; Sympathetic Nervous System ; Weight Gain

OBJECTIVEMany studies have shown that glucocorticoids play a crucial role in the development of obesity and insulin resistance. This study investigated the therapeutic effects of long-term inhibition of glucocorticoid activity on obesity and insulin resistance.

METHODSFour-week-old male Sprague-Dawley (SD) rats were randomly fed with a high-fat diet (fat content accounting for 20% of total calorie) (control group, n=8) or with a high-fat diet along with glycyrrhetic acid (GE, 800 mg/L), an inhibitor of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) for 24 weeks (GE-treated group, n=9). The body weights and the amount of food intake were monitored weekly and daily, respectively. After 24 weeks of GE treatment, oral glucose tolerance tests were performed. Blood glucose was measured by glucose oxidase method. The levels of plasma glucocorticoids, insulin and leptin were measured with radioimmunoassay. The levels of serum cholesterol and triglyceride were determined with an automatic measuring analyzer.

RESULTSThe food intake amount decreased significantly in the GE-treated group from 6 weeks and body weight gain was markedly less from 8 weeks after GE administration compared with the control group. After 24 weeks of treatment, the plasma levels of leptin and insulin in GE-treated rats were significantly reduced compared with the control group. The serum levels of cholesterol and triglyceride decreased markedly compared with the control group and the levels of blood glucose were significantly lower 15, 30, 60 and 120 minutes after oral glucose load in the GE-treated group compared with the control group.

CONCLUSIONSLong-term GE treatment may contribute to resisting diet-induced obesity and insulin resistance.

11-beta-Hydroxysteroid Dehydrogenases ; antagonists & inhibitors ; Animals ; Body Weight ; drug effects ; Dietary Fats ; administration & dosage ; Enzyme Inhibitors ; pharmacology ; Glucocorticoids ; physiology ; Glucose Tolerance Test ; Glycyrrhetinic Acid ; pharmacology ; therapeutic use ; Insulin ; blood ; Insulin Resistance ; Leptin ; blood ; Male ; Obesity ; drug therapy ; Rats ; Rats, Sprague-Dawley