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 multifunctional nature of the somatostatin (SS) family of peptides results from a multifaceted signaling system consisting of many forms of SS peptides that bind to a variety of receptor (SSTR) subtypes. Research in fish has contributed important information about the components, function, evolution, and regulation of this system. Somatostatins or mRNAs encoding SSs have been isolated from over 20 species of fish. Peptides and deduced peptides differ in their amino acid chain length and/or composition, and most species of fish possess more than one form of SS. The structural heterogeneity of SSs results from differential processing of the hormone precursor, preprosomatostatin (PPSS), and from the existence of multiple genes that give rise to multiple PPSSs. The PPSS genes appear to have arisen through a series of gene duplication events over the course of vertebrate evolution. The numerous PPSSs of fish are differentially expressed, both in terms of the distribution among tissues and in terms of the relative abundance within a tissue. Accumulated evidence suggests that nutritional state, season/stage of sexual maturation, and many hormones [insulin (INS), glucagon, growth hormone (GH), insulin-like growth factor-I (IGF-I), and 17beta-estradiol (E2)] regulate the synthesis and release of particular SSs. Fish and mammals possess multiple SSTRs; four different SSTRs have been described in fish and several of these occur as isoforms. SSTRs are also wide spread and are differentially expressed, both in terms of distribution of tissues as well as in terms of relative abundance within tissues. The pattern of distribution of SSTRs may underlie tissue-specific responses of SSs. The synthesis of SSTR mRNA and SS-binding capacity are regulated by nutritional state and numerous hormones (INS, GH, IGF-I, and E2). Accumulated evidence suggests the possibility of both tissue- and subtype-specific mechanisms of regulation. In many instances, there appears to be coordinate regulation of PPSS and of SSTR; such regulation may prove important for many processes, including nutrient homeostasis and growth control.
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PMID:Regulation of somatostatins and their receptors in fish. 1586 56

Dietary restriction of calories (caloric restriction [CR]) increases longevity in phylogenetically diverse species. CR retards or prevents age-dependent deterioration of tissues and an array of spontaneous and chemically induced diseases associated with obesity including cardiovascular disease, diabetes, and cancer. An understanding of the molecular mechanisms that underlie the beneficial effects of CR will help identify novel dietary, pharmacological, and lifestyle strategies for slowing the rate of aging and preventing these diseases as well as identify factors which modulate chemical toxicity. Here, we review the involvement of transcriptional coactivator proteins, peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 (PGC-1) alpha and beta, and regulated nuclear receptors (NR) in mediating the phenotypic changes found in models of longevity which include rodent CR models and mouse mutants in which insulin and/or insulin-like growth factor-I signaling is attenuated. PGC-1alpha is transcriptionally or posttranslationally regulated in mammals by: 1) forkhead box "other" (FoxO) transcription factors through an insulin/insulin-like growth factor-I -dependent pathway, 2) glucagon-stimulated cellular AMP (cAMP) response element binding protein, 3) stress-activated kinase signaling through p38 mitogen-activated protein kinase, and 4) the deacetylase and longevity factor sirtuin 1 (SIRT1). PGC-1alpha and PGC-1beta regulate the ligand-dependent and -independent activation of a large number of NR including PPARalpha and constitutive activated receptor (CAR). These NR regulate genes involved in nutrient and xenobiotic transport and metabolism as well as resistance to stress. CR reverses age-dependent decreases in PGC-1alpha, PPARalpha, and regulated genes. Strategies that target one or multiple PGC-1-regulated NR could be used to mimic the beneficial health effects found in models of longevity.
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PMID:Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity. 1642 81

Three hundred twenty Cobb 500 broiler breeder pullets at 21 wk of age were selected from a flock fed according to Cobb Breeder Management Guide specifications. One hundred sixty pullets at 21 wk of age were switched to ad libitum feeding, and the remaining 160 pullets continued to be control-fed. The pullets were photostimulated at 22 wk and maintained until 36.5 wk. Plasma samples were obtained, BW was determined, and hens were killed for determination of body composition at the following periods: 24 h prior to photostimulation, 2.5 wk after photostimulation, 24 h after first egg, and 36.5 wk following peak egg production. Compared with ad libitum-fed breeders, the restricted breeders had a higher percentage carcass protein and lower percentage carcass fat at all sampling periods. Total egg numbers were greater, and abnormal eggs were less for the restricted pullets compared with the ad libitum-fed pullets at 36.5 wk. Carcass percentage fat of ad libitum-fed pullets was positively related to plasma glucagon, insulin-like growth factor-II (IGF-II), and 17beta-estradiol but negatively related to plasma insulin, insulin/glucagon M ratio, insulin-like growth factor-I (IGF-I), thyroxine (T4), and triiodothyronine (T3). Carcass percentage fat of feed-restricted pullets was negatively related to IGF-I, IGF-II, and T4. The T4 was the most important hormone for predicting the percentage carcass fat in ad libitum-fed pullets, and IGF-I was the most important hormone for predicting the percentage carcass fat in feed-restricted pullets. The percentage carcass protein for ad libitum-fed breeders was positively correlated to IGF-I, T4, T3, insulin/glucagon M ratio, and insulin. Carcass percentage protein for feed-restricted breeders was positively correlated to IGF-I, IGF-II, T4, and glucagon. Stepwise regressions for predicting percentage carcass protein for breeders fed by both systems shows that T3 and IGF-I concentrations were the most important for ad libitum-fed breeders, whereas IGF-II and T4 were best for feed-restricted breeders. The hormone status of breeders may be a key indicator to help predict the body composition and thus support management decisions for maintaining optimum production.
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PMID:The relationship of body composition, feed intake, and metabolic hormones for broiler breeder females. 1683 Aug 57

Exercise-induced growth hormone (GH) secretion may significantly modulate growth and development in children. Altered physiological GH responses, therefore, may reduce the beneficial effects of exercise. High-fat food ingestion before exercise blunts the GH response in adults, but it is unknown whether this occurs in children. We therefore performed standard exercise tests, following a high-fat meal or placebo, in 12 children, age 11-15 (6 M, 6 F). GH, insulin-like growth factor-I, glucose, insulin, glucagon, cortisol, epinephrine and interleukin-6 samples were drawn at baseline, end-exercise, and 30 and 60 min post-exercise. While GH was similar at baseline in all experiments, the exercise-induced GH peak was lower after the high-fat meal (6.7 +/- 1.6 ng/l vs 11.8 +/- 2.4 ng/l, p <0.02). Other exercise responses were not affected by prior fat ingestion. A high-fat meal before exercise, therefore (a common event in Western societies), may reduce the growth factor response to exercise in children, with potential implications for growth and development.
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PMID:Effect of a high-fat meal on the growth hormone response to exercise in children. 1688 85

Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.
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PMID:Laron syndrome. First report from Greece. 1700 11

Developmental hormonal changes in Cobb 500 chick embryos and hatched chicks were determined by measuring plasma insulin, glucagon, insulin-like growth factor (IGF)-I, IGF-II, triiodothyronine, thyroxine, and glucose concentrations at different ages of embryogenesis and posthatch development. Plasma samples were obtained daily from 10 d of embryogenesis (10E) through 13 d posthatch and also at 17 and 21 d posthatch. A significant increase in plasma insulin was observed with increasing age from 10E to hatch. Plasma glucagon levels remained low until 17E, and then significantly increased approximately 3-fold at hatch, which corresponded with increasing plasma glucose levels during late embryo development. The plasma insulin to glucagon molar ratio of incubation from 14E to 17E ranged from 2 to 4, and was significantly higher than at any other time during incubation. These results indicate that insulin may be an important promoter of chick embryonic growth by the anabolic drive to promote protein deposition. Insulin and glucagon increased after hatch, which may be due to increased feed consumption and increased utilization of carbohydrates as the key energy source, compared with nutrients obtained through lipolysis and proteolysis in the embryos. Plasma triiodothyronine increased 4-fold from 18E to 20E, and thyroxine increased 3-fold from 16E to 19E. Insulin-like growth factor-I and IGF-II peaked at 14E. Insulin-like growth factor-I steadily increased above embryonic levels during the 3 wk of the posthatch period, whereas IGF-II levels steadily declined. These results suggest that IGF-II may be a more important functionary for chick embryonic development than IGF-I, and that IGF-I may be more important than IGF-II after hatch. The profile of metabolic hormones in the present study may help support an understanding of significant changes that occur in embryonic development and posthatch growth in chicks.
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PMID:Developmental changes of plasma insulin, glucagon, insulin-like growth factors, thyroid hormones, and glucose concentrations in chick embryos and hatched chicks. 1736 38

A trial was conducted to determine the effects of different feeding regimens on plasma hormone and metabolite levels in 16-wk-old broiler breeder pullets. A flock of 350 Cobb 500 breeder pullets was divided in 2 at 28 d of age and fed either every day (ED, 5 pens of 35 birds) or skip-a-day (SKIP, 5 pens of 35 birds) from 28 to 112 d of age. Total feed intake did not differ between the 2 groups. At 112 d, 52 randomly selected pullets from the larger flock of ED-fed pullets, and 76 from the SKIP-fed pullets were individually caged and fed a meal of 74 g (ED) or 148 g (SKIP). Blood samples were collected from 4 pullets in each group by cardiac puncture at intervals after feeding. Plasma was analyzed for insulin, glucagon, insulin-like growth factor-I and insulin-like growth factor-II, triiodothyronine and thyroxine, corticosterone, leptin, glucose, nonesterified fatty acids, triglycerides, and uric acid. Feed retention in the crop was also noted at each interval. In ED birds, the crop was empty by 12 h and in SKIP birds, the crop was empty by 24 h after feeding. The physiological responses to fasting, such as increased glucagon and corticosterone and reduced plasma triglyceride, occurred at times coincidental with crop emptying in both ED and SKIP birds. Overall, mean insulin-like growth factor-I levels were higher (P < 0.05) in ED birds. Triiodothyronine was higher (P = 0.09) in SKIP birds. Overall mean plasma corticosterone was 2-fold higher in SKIP-fed birds, which may be related to the increased length of fasting periods, hunger, and stress. Plasma leptin was consistently higher in ED-fed birds, which was indicative of their more consistent food supply and more stable energy status. In summary, the experiment reported here shows that different feeding regimens can alter hormone and metabolite profiles, in spite of total feed intakes being equal.
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PMID:An examination of the role of feeding regimens in regulating metabolism during the broiler breeder grower period. 2. Plasma hormones and metabolites. 1821 69

In previous studies, high plasma insulin was associated with earlier resumption of postpartum estrous cycles in dairy cows. The objective of this experiment was to quantify hormonal and ovarian responses to dietary starch and fat contents. Thirty cows were fed on a standard diet from calving until 40 d in milk (DIM) and then 6 cows were allocated to each of 5 isoenergetic diets containing 231, 183, 159, 135, and 87 g of starch and 39, 42, 43, 45, and 48 g of fat/kg of dry matter (DM) for diets 1 to 5, respectively, until 70 DIM. Estrus was synchronized at 60 DIM. Between 60 and 70 DIM, energy intake, milk yield, and energy balance were similar among diet groups. Plasma insulin-to-glucagon ratio increased with increasing dietary starch and decreasing dietary fat concentrations, reaching a break point at 159 g of starch, 43 g of fat/kg of DM (diets 1 to 5: mean 3.86, 3.78, 3.59, 2.98, 2.06 +/- standard error 0.22). Growth hormone, insulin-like growth factor-I, and leptin did not vary among diets. The greatest dietary starch concentration was associated with elevated plasma urea-N (diets 1 to 5: mean 3.69, 3.01, 2.94, 2.95, 2.75, +/- standard error 0.13 mmol/L, respectively) and delayed postovulatory progesterone increase (progesterone at 3 to 5 d postovulation for diets 1 to 5: mean 2.7, 5.9, 4.2, 5.6, 4.3 +/- standard error 0.9 ng/mL, respectively). The number of small (<5 mm) ovarian follicles was positively related to starch intake (r = 0.381) and plasma insulin concentration (r = 0.402). It is concluded that to maintain adequate insulin-to-glucagon ratio in cows at the start of the breeding period, dietary starch concentration should be above 160 g/kg of DM and dietary fat below 44 g/kg of DM, and this should have a positive effect on ovarian function.
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PMID:Nutrition, metabolism, and fertility in dairy cows: 1. Dietary energy source and ovarian function. 1883 3

Plasma insulin has important implications for ovarian function in dairy cows. Previous work demonstrated that plasma insulin increased with increasing dietary starch and decreasing dietary fatty acid concentrations. The objective of this experiment was to investigate hormonal and ovarian responses to dietary fatty acid content with no change in other dietary components. Thirty cows were fed a standard diet from calving until 40 d in milk (DIM) and then 6 cows were transferred to each of 5 diets containing 0, 8, 15, 23, and 30 g/kg of dry matter (DM) of calcium salts of palm fatty acids (CaPFA; Megalac) until 70 DIM. Estrus was synchronized at 60 DIM. Between 60 and 70 DIM, energy intake, milk yield, and energy balance were similar among diet groups. Plasma insulin decreased when dietary concentration of CaPFA exceeded 15 g/kg of DM (insulin: 0.46, 0.41, 0.46, 0.33, 0.28 +/- SE 0.034 ng/mL for diets containing 0 to 30 g of CaPFA/kg of DM, respectively). Maximum plasma insulin to glucagon ratio was observed with 15 g of CaPFA/kg of DM (ratios: 3.99, 4.33, 4.67, 3.45, 2.89 +/- SE 0.156 for diets containing 0 to 30 g of CaPFA/kg of DM, respectively). Plasma concentrations of growth hormone, insulin-like growth factor-I and leptin did not vary between diets. The number of small (<5 mm) ovarian follicles was negatively related to plasma insulin concentration (r = -0.328) and was stimulated by CaPFA supplementation at all rates tested compared with cows receiving zero CaPFA (small follicles preovulation: 6.7, 11.2, 11.5, 11.3, 11.9 +/- SE 1.48 for diets containing 0 to 30 g of CaPFA/kg of DM, respectively). The number of medium-sized follicles, and diameters of the ovulatory follicles and corpora lutea, were not affected by CaPFA supplementation. It is concluded that dietary total fat concentration should be below 50 g/kg of DM to avoid depressing plasma insulin concentration in cows at the start of the breeding period.
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PMID:Nutrition, metabolism, and fertility in dairy cows: 2. Dietary fatty acids and ovarian function. 1883 4

Therapeutics based on the actions of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), have recently been introduced for the treatment of type 2 diabetes mellitus. The serine/threonine kinase Akt is a major mediator of incretin action on the pancreatic islet, increasing beta-cell mass and function and promoting beta-cell survival. The mechanisms underlying incretin activation of Akt are thought to involve an essential phosphoinositide 3-kinase-mediated phosphorylation of threonine 308, similar to the prototypical Akt activator, insulin-like growth factor-I (IGF-I). In this study, using activity assays on immunoprecipitated Akt, we discovered that GIP and GLP-1 were capable of stimulating Akt in the INS-1 beta-cell line and isolated mouse islets via a mechanism that did not require phosphoinositide 3-kinase or phosphorylation of Thr(308) and Ser(473), and this pathway involved the production of cAMP. Furthermore, we found that GIP stimulated anti-apoptotic signaling via this alternate mode of Akt activation. We conclude that incretins can activate Akt via a novel noncanonical mechanism that may provide an alternative therapeutic target for the treatment of type 2 diabetes mellitus and have broader implications for Akt physiology in human health and disease.
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PMID:Noncanonical activation of Akt/protein kinase B in {beta}-cells by the incretin hormone glucose-dependent insulinotropic polypeptide. 1923 42


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