Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the gene for phosphoenolpyruvate carboxy-kinase (PEPCK) is stimulated by thyroid hormone (T3), glucagon (via cyclic AMP) and glucocorticoids. A region of the PEPCK promoter between -332 and -308 mediates the induction of transcription by T3. To characterize this region further, mutations were introduced into this region of the PEPCK promoter and the modified promoters ligated to the chloramphenicol acetyltransferase (CAT) reporter gene. Using these PEPCK-CAT vectors in transient transfections in HepG2 cells, it was found that T3 stimulates PEPCK transcription through two direct repeats of the AGGTCA motif located between nucleotides -330 and -319 [PEPCK-thyroid-hormone-responsive element (TRE)]. The beta form of the T3 receptor (TR beta) bound PEPCK-TRE as a homodimer but bound far more efficiently as a heterodimeric complex with the retinoid X receptor (RXR). An additional region called P3(I) (-250 to -234) is required for T3 responsiveness and binds members of the CCAAT-enhancer-binding protein (C/EBP) family. P3(I) contains an AGGTCA-like motif that can bind the TR beta-RXR heterodimer. Mutagenesis of this motif abolished TR beta-RXR binding without reducing T3 induction. Mutation of the C/EBP-binding site or insertion of a cyclic AMP-responsive-binding-protein site at P3(I) eliminated the T3 response. Our results indicate that T3 stimulation of PEPCK transcription is mediated by TR beta bound to PEPCK-TRE and requires C/EBP to be bound at the P3(I) site.
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PMID:Regulation of phosphoenolpyruvate carboxykinase gene transcription by thyroid hormone involves two distinct binding sites in the promoter. 763 10

Hormonal and non-hormonal regulation of glucokinase gene expression was investigsted in cultured rat islet cells. To measure glucokinase mRNA in pancreatic islet cells, the competitive PCR method was adopted. With this method, GKmRNA levels can be measured using only 0.1-1.0 microgram of total RNA isolated from cultured rat islet cells. Following 24 h preculture with 5.5 mM glucose, islet cells were cultured for 24 or 8 h with hormonal or non-hormonal factors. Glucokinase mRNA levels tended to increase, but not significantly, at 16.7 mM glucose compared to those at 5.5 mM glucose. Treatment with either 1 microM T3 or 1 microM glucagon resulted in a decrease in the glucokinase mRNA level with 16.7 mM glucose, whereas 1 microM insulin had no effect on glucokinase mRNA. Five mM dibutyryl cyclic AMP decreased the glucokinase mRNA level with 16.7 mM glucose, but cycloheximide did not block this inhibitory effect, suggesting that the effect of glucagon may be mediated by cyclic AMP and that protein synthesis is not involved in the response. Furthermore, the islet glucokinase mRNA level increased in response to 1 microM glibenclamide with 5.5 mM glucose and the response was abolished by cycloheximide, which indicates the involvement of protein synthesis in the glibenclamide-induced mRNA change. An 8-bromo-cyclic GMP (1 microM) and vanadate (1 microM) did not affect the islet GKmRNA level. These findings suggested that thyroid hormone and glucagon-cyclic AMP suppress, and glibenclamide increases the GKmRNA level in cultured rat islet cells, and that insulin, cyclic GMP and vanadate differentially affect glucokinase gene expression in pancreatic islet cells and in the liver.
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PMID:Regulation of glucokinase gene expression in cultured rat islet cells: the inhibitory effects of T3 and glucagon, and the stimulatory effect of glibenclamide. 766 33

A large body of literature indicates that protein from soybeans reduces blood cholesterol concentrations in experimental animals as well as in humans. The mechanism and component of soy responsible has not been established fully. Some suggest that when soy protein is fed, cholesterol absorption and/or bile acid reabsorption is impaired. This is observed in some animal species, such as rabbits and rats, but not in humans nor when amino acids replace intact soy protein. Others propose that changes in endocrine status, such as alteration in insulin:glucagon ratio and thyroid hormone concentrations, are responsible. The metabolic changes that have been observed on soy protein feeding in a variety of animal models, and in some cases humans, include increased cholesterol synthesis, increased bile acid synthesis (or fecal bile acid excretion), increased apolipoprotein B or E receptor activity and decreased hepatic lipoprotein secretion and cholesterol content, which are associated with an increased clearance of cholesterol from the blood. One hypothesis suggests amino acid composition or proportionality of soy causes changes in cholesterol metabolism (possibly via the endocrine system). Others have proposed that nonprotein components (such as saponins, fiber, phytic acid, minerals and the isoflavones) associated with soy protein affect cholesterol metabolism either directly or indirectly.
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PMID:Overview of proposed mechanisms for the hypocholesterolemic effect of soy. 788 41

The phenomenon of clinical improvement of diabetes mellitus after occurrence of pituitary insufficiency has been reported occasionally in the medical literature, as a human counterpart of Houssay's experiment with hypophysectomized diabetic animals. We report the case of a 76-year-old woman who developed diabetes in 1928, at the age of 14, and was treated with low doses of insulin. At the age of 29, during the 7th month of her second pregnancy, she suddenly developed severe headaches and soon afterwards an intense polyuria which subsided under treatment with posterior pituitary extract. Her pregnancy followed to term but uterine stimulants had to be used at delivery because of lack of contractions. She was unable to nurse her baby and a permanent amenorrhea ensued. She continued using the posterior pituitary powder for several years, after which she discontinued it without adverse effects. The dose of insulin was decreased gradually until its replacement by chloropropamide in 1967 and glibenclamide in 1970. The present dose of glibenclamide is 2.5 mg daily, on which she has occasional mild hypoglycemic reactions. When the medication was discontinued for 5 days glycemia rose to 450 mg/dl but responded immediately to 2.5 mg of the drug with a mild hypoglycemia. She never required thyroid hormone therapy. Glucocorticoid substitution was instituted recently because of evidence of mild adrenocortical insufficiency. Basal hormone levels were normal for thyroxin, thyrotropin, FSH, LH, prolactin, hGH and cortisol; the responses to pituitary stimulation with TRH and LHRH were subnormal or nil. Cortisol stimulation with ACTH was normal. Insulin levels rose moderately after stimulation with glucagon, and with glibenclamide, with simultaneous marked decrease in glycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Houssay's phenomenon in man]. 820 16

We previously demonstrated that hyperglucagonemia may be responsible for thyroid hormone alterations noted in some nonthyroidal illnesses. Since TSH secretion is also known to be altered in many subjects with several nonthyroidal illnesses, we assessed the influence of sustained hyperglucagonemia on TSH secretory pattern in 5 anesthetized dogs. Serum TSH concentrations were determined after a 16-h fast and again at intervals of 15 min during sustained hyperglucagonemia (515-645 pg/mL) induced by iv bolus administration of glucagon 0.1 mg followed by a continuous glucagon infusion 3 ng/kg/min for 3 h. TRH (200 micrograms) was administered iv at 60 min to assess the influence of sustained hyperglucagonemia on the hypothalamic pituitary thyrotroph axis during the study. A control study was also conducted using normal saline instead of glucagon, and both studies were performed in a randomized sequence. Basal TSH levels were not significantly different during both studies. However, serum TSH declined significantly during sustained hyperglucagonemia prior to TRH administration (delta TSH, pre-TRH, -0.86 +/- 0.24 vs 0.02 +/- 0.07 ng/mL for normal saline, p < 0.01). Furthermore, TSH response to iv TRH administration was significantly blunted during glucagon infusion alone as expressed by both the absolute rise (delta TSH, post-TRH, 1.1 +/- 0.5 vs 5.9 +/- 1.7 ng/ml for normal saline, p < 0.01) as well as an integrated response over a 2-h period (sigma TSH, post-TRH, 4.0 +/- 1.1 vs 11.7 +/- 3.5 ng/min/mL, p < 0.001). Therefore, this study demonstrates that sustained hyperglucagonemia inhibits basal TSH secretion as well as TSH response to iv TRH administration, a TSH secretory pattern similar to that noted at the peak of many nonthyroidal illnesses.
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PMID:Impaired TSH secretion during sustained hyperglucagonemia in anesthetized dogs. 856 78

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P < .05; area under the curve [AUC] for OGTT, 7.7 +/- 0.3 v 6.7 +/- 0.4 mmol/L min, P < .01) without any change in plasma insulin levels. After T3 administration, plasma glucagon levels were lower than at baseline (basal, 92 +/- 7 v 148 +/- 35 ng/L; AUC, 74 +/- 6 v 98 +/- 16 ng/L.min, P < .05), showing an appropriate reduction by the increased glucose levels. Conversely, plasma GH showed impaired suppression by hyperglycemia (AUC, 1.2 +/- 0.3 v 0.7 +/- 0.2 microgram/L.min, P < .05). In conclusion, thyroid hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.
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PMID:Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism. 876 64

The effects of hypothalamic heating and cooling on thermoregulatory effector activities, lipid and carbohydrate metabolism, insulin, glucagon, thyroxine, arginine vasopressin (AVP) and cortisol were investigated in conscious rabbits and compared with those obtained in the febrile state. The study shows that under control conditions hypothalamic heating lowers, and cooling raises core temperature. Core temperature always rose to similar degrees in response to bacterial lipopolysaccharide (LPS) during an observation time of 150 min, but it started to rise from lower and higher levels, respectively, during hypothalamic heating and cooling. The effects of hypothalamic thermal stimulation on specific thermoregulatory effector activities support the conclusion that, within 60 min after LPS, the hypothalamic warm signal input is reduced relative to the cold signal input. The increase of thyroxine levels following LPS suggests that the elevation of the thermoregulatory setpoint was caused by an increased input of hypothalamic TRH neurons, known to induce the full autonomic pattern of cold defense also in response to non-thermal stimuli. With the exception of an increase of glucagon during hypothalamic cooling at control conditions, hypothalamic thermal stimulation alone did not alter lipid and carbohydrate metabolism, insulin, thyroid hormone, AVP and cortisol secretion. A spontaneous heat loss effector response separated the first from the second fever phase 60 min after LPS. Subsequently AVP and cortisol plasma levels rose in febrile animals, irrespective of hypothalamic heating and cooling, presumably as a consequence of pyrogenic activation of corticotropin releasing factor (CRF) producing neurons and their reciprocal interaction with TRH neurons on the one hand, and by a reciprocal interaction of the latter with AVP neurons on the other.
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PMID:Hormonal secretion patterns but not autonomic effector responses elicited by hypothalamic heating and cooling are altered in febrile rabbits. 896 49

A continuous turnover of protein (synthesis and breakdown) maintains the functional integrity and quality of skeletal muscle. Hormones are important regulators of this remodeling process. Anabolic hormones stimulate human muscle growth mainly by increasing protein synthesis (growth hormone, insulin-like growth factors, and testosterone) or by decreasing protein breakdown (insulin). Unlike in growing animals, insulin's main anabolic effect on muscle protein in adult humans is an inhibition of protein breakdown. Protein synthesis is stimulated only in the presence of a high amino acid supply. A combination of the stress hormones (glucagon, glucocorticoids, and catecholamines) cause muscle catabolism, but the effects of the individual hormones on human muscle and their mechanisms of action remain to be clearly defined. Although thyroid hormone is essential during growth, both an excess and a deficiency cause muscle wasting by yet unknown mechanisms. A greater understanding of the regulation of human muscle protein metabolism is essential to elucidate mechanisms of muscle wasting.
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PMID:Hormonal regulation of human muscle protein metabolism. 924 Sep 36

This study examined the hypocholesterolemic effect and hormonal changes resulting from 30 d of supplementation with Vicia faba L. (field bean) flour of diets of young men (aged 18-21 y; n = 40) with borderline-high or high serum cholesterol values. All subjects (groups A-D) consumed the same basic diet. Additionally, volunteers in the control group (A) consumed 90 g control flour/d whereas those in the three bean groups received either 90 g cooked field bean flour (groups B and C) or 90 g raw field bean flour (group D) daily. Groups A and B included volunteers with borderline-high cholesterol values [5.2-6.2 mmol total cholesterol/L and 3.4-4.1 mmol low-density-lipoprotein (LDL) cholesterol/L]. Subjects in groups C and D had high serum cholesterol concentrations (total cholesterol > 6.2 mmol/L and LDL cholesterol > 4.1 mmol/L). After 30 d, serum glucose, insulin, triacylglycerol, total, LDL-cholesterol, and very-low-density-lipoprotein (VLDL)-cholesterol values were significantly lower than initial values in all subjects who consumed diets containing field bean flour (P < or = 0.0001, except for LDL-cholesterol concentrations in group C, for which P < or = 0.0007). Legume intake also resulted in a significant increase (P < or = 0.0001) in glucagon and high-density-lipoprotein cholesterol. Neither cortisol nor thyroid hormone values changed significantly. The results suggest that the hypocholesterolemic effect of field bean intake depends at least partly on a concomitant increase in glucagon and decrease in insulin values. The more marked reduction in triacylglycerol and VLDL-cholesterol concentrations in subjects who consumed raw field beans indicates a coparticipation of their thermolabile components.
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PMID:Hormonal implications of the hypocholesterolemic effect of intake of field beans (Vicia faba L.) by young men with hypercholesterolemia. 939 99

The CYP genes encode enzymes of the cytochrome P-450 superfamily. Cytochrome P-450 (CYP) enzymes are expressed mainly in the liver and are active in mono-oxygenation and hydroxylation of various xenobiotics, including drugs and alcohols, as well as that of endogenous compounds such as steroids, bile acids, prostaglandins, leukotrienes and biogenic amines. In the liver the CYP enzymes are constitutively expressed and commonly also induced by chemicals in a characteristic zonated pattern with high expression prevailing in the downstream perivenous region. In the present review we summarize recent studies, mainly based on rat liver, on the factors regulating this position-dependent expression and induction. Pituitary-dependent signals mediated by growth hormone and thyroid hormone seem to selectively down-regulate the upstream periportal expression of certain CYP forms. It is at present unknown to what extent other hormones that also affect total hepatic CYP activities, i.e. insulin, glucagon, glucocorticoids and gonadal hormones, act zone-specifically. The expression and induction of CYP enzymes in the perivenous region probably have important toxicological implications, since many CYP-activated chemicals cause cell injury primarily in this region of the liver.
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PMID:Zonation of hepatic cytochrome P-450 expression and regulation. 940 71


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