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)

The aim of this study was to investigate the endocrine response to wintertime starvation in the male American mink (Mustela vison) fasted for 16 hrs, 2 days, 3 days, 5 days, or 7 days (n =10 per group). After 2 days of fasting, the plasma leptin concentrations decreased, along with the triiodothyronine, testosterone, and progesterone levels, and the blood monocyte counts. Leptin also seems to trigger the response to fasting in mustelids by inducing immunosuppression and downregulation of the reproductive and thyroid axes. The dramatic increase in the peptide YY concentrations after 3 days of fasting may be required to suppress gastrointestinal processes during food scarcity. The plasma insulin levels decreased, and those of glucagon increased after 5 days of fasting in association with efficient glucose sparing and lipid mobilization. Body energy stores cannot be wasted for growth during nutritional scarcity and, thus, the growth hormone levels of the minks decreased after 5 days of fasting. The plasma noradrenaline and cortisol concentrations also decreased after 3 and 7 days without food, respectively. The plasma ghrelin, adiponectin, resistin, thyroxine, adrenaline, or estradiol levels did not respond to fasting. The endocrine response to food deprivation is remarkably similar in divergent mammalian orders, indicating that the hormonal signals enhancing survival during nutritional scarcity must be evolutionarily old and well conserved.
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PMID:Endocrinologic adaptations to wintertime fasting in the male American mink (Mustela vison). 1617 29

Leptin reduces food intake in part by enhancing satiety responses to gastrointestinal signals produced in response to food consumption. Glucagon-like peptide 1 (GLP-1), secreted by the intestine when nutrients enter the gut, is one such putative satiety signal. To investigate whether leptin enhances the anorexic effects of GLP-1, rats received either saline or a subthreshold dose of leptin before intraperitoneal injection of either GLP-1 or Exendin-4 (Ex4; a GLP-1 receptor agonist). Leptin pretreatment strongly enhanced anorexia and weight loss induced by GLP-1 or Ex4 over 24 h. Conversely, fasting attenuated the anorexic response to GLP-1 or Ex4 treatment via a leptin-dependent mechanism, as demonstrated by our finding that the effect of fasting was reversed by physiological leptin replacement. As expected, Ex4 induced expression of c-Fos protein, a marker of neuronal activation, in hindbrain areas that process afferent input from satiety signals, including the nucleus of the solitary tract and area postrema. Unexpectedly, leptin pretreatment blocked this response. These findings identify physiological variation of plasma leptin levels as a potent regulator of GLP-1 receptor-mediated food intake suppression and suggest that the underlying mechanism is distinct from that which mediates interactions between leptin and other satiety signals.
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PMID:Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulation. 1713 Apr 84

In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.
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PMID:Insulin counter-regulatory factors, fibrinogen and C-reactive protein during olanzapine administration: effects of the antidiabetic metformin. 1729 6

Leptin interplays with other peptides to control feeding behaviour in humans and animals. Using exendin-4, an agonist of glucagon-like peptide-1, we investigated whether leptin modifies its effect on food intake in the rat. In the first series, exendin-4 alone (0.1, 2 or 10 microg per rat), leptin alone (0.1, 2, 10 or 100 microg per rat) or exendin-4 and leptin together (0.1 + 0.1, 2 + 2, 10 + 10, or 2 + 100 microg per rat, respectively) were injected once intraperitoneally. In the second series animals were injected either with exendin-4 (2 microg) alone, leptin (10 microg) alone, or leptin (10 microg) + exendin-4 (2 microg) daily for 5 subsequent days. At the lowest dose used, leptin and exendin-4 injected once together, but not separately, reduced significantly a 24-hour food intake. When used in higher doses, however, leptin did not change the exendin-4-dependent suppressory effect on food consumption. No significant differences in food intake were seen between rats treated repeatedly with exendin-4 only and animals injected with both drugs. Hence, leptin and exendin-4 may act additively to inhibit appetite when present in low concentrations while, at high leptin doses, this effect is abolished. The lack of synergistic effects of exendin-4 and high leptin concentrations on food intake may explain, at least in part, mechanisms responsible for leptin resistance in subjects with hyperleptinaemia.
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PMID:Interactions between leptin and exendin-4, a glucagon-like peptide-1 agonist, in the regulation of food intake in the rat. 1762 2

Body mass--strictly speaking: the adipose tissue mass--is regulated in a feed-back system by the hypothalamus and brainstem, where adiposity signals (leptin, insulin, amylin) and intestinal peptides (ghrelin, PYY, PP, GLP-1, OXM, CCK) and the vagal nerve provide afferent information to the central controller on the size of white adipose tissue and the actual nutritional state, respectively. Two distinct groups of neurons in the arcuate nucleus accept and process the afferent information provided by leptin produced by white adipocytes in proportion to their mass. Leptin binding to the leptin-receptors on the surface of these neurons initiates intracellular signal transduction and activation of target genes, resulting in the synthesis and release of neuropeptides (POMC, CART) with anorectic effects. Secondary centers in the brain are also activated, and finally integrated effector mechanisms are generated in order to regulate the balance between energy intake and expenditure. The regulation of body weight is carried out by the central nervous system in a complex and redundant way, characterized by interconnections and overlaps with other neuroendocrine functions, such as growth, thyroid and adrenal function, memory, addictive and reward mechanisms. Targeting one or another component of this complicated system with drugs might result in interference with other systems and functions, so the occurrence of adverse events is probable. The worldwide epidemic of obesity--resulting mostly from the abundance of energy-dense foods and sedentary lifestyle coupled with a regulatory system unable to cope with this environment--has resulted in a continuous increase of research activities in both academic and industrial centers to develop new drugs and treatment strategies beyond lifestyle changes (diet, physical activity and behavioral therapy) to fight obesity more effectively.
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PMID:[The regulation of body mass and its relation to the development of obesity]. 1789 Jan 70

The central targets mediating the anorectic and other actions of leptin have yet to be fully identified. Although previous studies focused on the hypothalamus, leptin also acts on neurons in extrahypothalamic sites, including the nucleus of the solitary tract (NTS). Moreover, injection of leptin into the NTS of rats suppresses food intake. Within the central nervous system, glucagon-like peptide (GLP-1), a product of proglucagon, is synthesized almost exclusively in neurons of the NTS. Intracerebroventricular administration of GLP-1 inhibits energy intake, and GLP-1 receptor antagonists attenuate the anorexic effects of leptin in rats. To examine whether NTS proglucagon neurons are directly regulated by leptin, we performed double GLP-1 and phosphorylation of signal transducer and activator of transcription-3 immunohistochemistry on brain sections from ip leptin-treated mice and rats. Leptin induced phosphorylation of signal transducer and activator of transcription-3 in 100% of GLP-1 cells in the caudal brainstem of mice. In striking contrast, 0% of GLP-1-positive neurons in rats responded to leptin. We then measured regulation of NTS proglucagon mRNA using real-time RT-PCR in mice and rats fed ad libitum, fasted, or fasted and treated ip with leptin. In mice, proglucagon mRNA fell by fasting, and this was prevented by leptin administration. In rats, by contrast, proglucagon mRNA was unaffected by either fasting or leptin. Taken together, our studies reveal direct regulation of proglucagon neurons by leptin in mice but not rats along with corresponding species differences in the regulation of proglucagon mRNA expression. These data, combined with previous results, suggest a different mechanism of interaction between leptin and NTS proglucagon neurons in mice and rats.
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PMID:Divergent leptin signaling in proglucagon neurons of the nucleus of the solitary tract in mice and rats. 1797 23

The various hormones, proteins and other compounds related to developing obesity, insulin resistance and type 2 diabetes are analyzed in the paper. 1) Leptin, ciliary neurutrophic factor, adiponectin, glucagon-like peptide 1, peptide YY, neuromedin S, as well as the protein receptors of these hormones decrease the food consumption, increase the energy turnover, and prevent obesity, insulin resistance, and type 2 diabetes development. The mediators of these hormone and receptor actions are melanocyte stimulating hormone (MSH), corticotropin-releasing hormone (CRH), and the others. 2) Ghrelin, endogenose cannabinoides, galanin-like peptide and the mediators of their actions: neuropeptide Y (NPY) and Agouti gene related protein (AGRP) increase the appetite and food consumption. Peroxisome proliferation-activated receptor (PPAR) performs the similar action on food intake. The activation of the first group compound functioning decreases the obesity, increases the energy turnover, facilitates the insulin action and prevents the insulin resistance and type 2 diabetes. Increasing the activities of the second group, as well as, decreasing the actions of the first one of substances induce the opposite effects and facilitate obesity, insulin resistance, and type 2 diabetes developments. The interconnections of the molecular mechanisms of so many hormone actions make the very complicated tusk to study the various endocrine disorders including diabetes mellitus as well.
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PMID:[The interconnections of molecular mechanisms of hormone actions and their role in pathogenesis of obesity, insulin resistance, and diabetes mellitus]. 1842 6

Zinc deficiency induces a striking reduction of food intake in animals. To elucidate the mechanisms for this effect, two studies were connectedly conducted to determine the effects of peripheral administration of zinc on food intake in rats fed the zinc-adequate or zinc-deficient diets for a 3-week period. In study 1, two groups of male Sprague-Dawley rats were provided diets made either adequate (ZA; 38.89 mg/kg) or deficient (ZD; 3.30 mg/kg) in zinc. In study 2, after feeding for 3 weeks, both ZA and ZD groups received intraperitoneal (IP) injection of zinc solution with three levels (0.5, 1.0, and 2.0 microg zinc/g body weight, respectively) and cumulative food intake at 0.5, 1, 2, 4, and 24 h, and plasma hormones concentrations were measured. The results in study 1 showed rats fed the ZD diets revealed symptoms of zinc deficiency, such as sparse and coarse hair, poor appetite, susceptibility to surroundings, lethargy, and small movements. Zinc concentrations in serum, femur, and skeletal muscle of rats fed the ZD diets declined by 26.58% (P < 0.01), 27.32% (P < 0.01), and 24.22% (P < 0.05), respectively, as compared with ZA control group. These findings demonstrated that rat models with zinc deficiency and zinc adequacy had been fully established. The results in study 2 showed that IP administration of zinc in both ZA and ZD rats did not influence food intake at each time points (P > 0.05), although zinc deficiency suppressed food intake. Plasma neuropeptide Y (NPY) was higher, but insulin and glucagon were lower in response to zinc deficiency or zinc administration by contrast with their respective controls (P < 0.05). Leptin, T3, and T4 concentrations were uniformly decreased (P < 0.05) in rats fed the ZD diets in contrast to ZA diets; however, no differences (P > 0.05) were observed during zinc injection. Calcitonin gene-related peptide was unaffected (P > 0.05) by either zinc deficiency or zinc administration. The present studies suggested that zinc administration did not affect short-term food intake in rats even in the zinc-deficient ones; the reduced food intake induced by zinc deficiency was probably associated with the depression in thyroid hormones. The results also indicated that NPY and insulin varied conversely during the control of food intake.
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PMID:The effect of peripheral administration of zinc on food intake in rats fed Zn-adequate or Zn-deficient diets. 1842 33

Hypothalamic neuronal histamine and its H(1) receptor (H(1)-R), a leptin signaling pathway in the brain, regulate body weight and adiposity by affecting food intake and energy expenditure. Glucagon-like peptide-1 and/or corticotrophin-releasing hormone mediate leptin signaling to neuronal histamine. Leptin-induced suppression of food intake and upregulation of uncoupling protein-1 expression in brown adipose tissue were partially attenuated in histamine H(1)-R knockout (H(1)KO) mice. H(1)KO mice developed maturity-onset obesity. Hyperphagia and decreased energy expenditure assessed by the expression of uncoupling protein-1 mRNA were observed in older (48-wk-old) obese H(1)KO mice but not in younger (12-wk-old) non-obese H(1)KO mice. However, the diurnal feeding rhythm was impaired even in younger non-obese animals. Specifically, disruption of the feeding rhythm developed before the onset of obesity in H(1)KO mice. Correction of these abnormal feeding rhythms with scheduled feeding improved the obesity and associated metabolic disorders in the H(1)KO mice. These findings suggest that histamine H(1)-R is crucial for regulating the feeding rhythm and in mediating the effects of leptin. Early disruption of H(1)-R-mediated functions in H(1)KO mice may lead to hyperphagia and decreased energy expenditure, which may contribute to the development of obesity in these animals.
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PMID:Hypothalamic neuronal histamine regulates body weight through the modulation of diurnal feeding rhythm. 1872 79

Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 min postmeal, and at 40 min postmeal. We found that hypoxia caused a significant elevation in plasma leptin levels (normoxia, 4.9 +/- 0.8 pg.mL-1; hypoxia, 7.7 +/- 1.5 pg.mL-1; p < 0.05; range, -16% to 190%), no change in the average GLP-1 response to hypoxia, and only a small trend toward an increase in GLP-1 levels 40 min postmeal (fasting, 15.7 +/- 0.9 vs 15.9 +/- 0.7 pmol.L-1; 20 min postmeal, 21.7 +/- 0.9 vs 21.8 +/- 1.2 pmol.L-1; 40 min postmeal, 19.5 +/- 1.2 vs. 21.0 +/- 1.2 pmol.L-1 for normoxia and hypoxia, respectively; p > 0.05 normoxia vs hypoxia). There was a correlation between SaO2 and leptin after the 17 h exposure (r = 0.45; p < 0.05), but no relation between SaO2 and GLP-1. These data confirm that leptin increases with hypoxic exposure in humans. Further study is needed to determine the influence of hypoxia and altitude on GLP-1 levels.
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PMID:Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans. 1892 68


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