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)

Cerebral magnetic resonance imaging findings are of great value for the diagnosis of nonacquired GH deficiency (GHD), and ectopic posterior pituitary hyperintense signal (EPPHS) is a sensitive and specific indicator of hypopituitarism. It has been suggested that patients with childhood-onset GHD and EPPHS do not require additional investigation of GH secretion and should not be retested when adult height is achieved. This recommendation has never been validated through a systematic study. This study aimed to characterize the anterior pituitary function status of patients with EPPHS treated for GHD during childhood after completion of GH therapy when adult height had been achieved. Patients (n = 18; 15 males and three females) with childhood-onset GHD associated with ectopic neurohypophysis were treated with hGH (0.20 +/- 0.05 mg/kg.wk) for 9.9 +/- 4.0 yr (from 6.8 +/- 4.7 to 17.7 +/- 1.3 yr of age) with a mean height gain of 2.6 +/- 1.4 sd score. GH secretion was reevaluated by arginine insulin (n = 15) or propanolol glucagon (n = 3) test after 0.5 +/- 0.6 yr of GH withdrawal. At reevaluation, peak GH was more than 10 mug/liter in four patients (22%; range, 11.7-19.5 microg/liter; group I), between 5 and 10 microg/liter in three patients (17%; range, 7.3-9 mug/liter; group II), and less than 5 microg/liter in 11 patients (61%; range, 0-4.7 microg/liter; group III). A positive correlation was found between serum IGF-I and peak GH levels after attainment of adult height (P = 0.007). Only one of the seven patients who showed increased GH secretion ability in adulthood (groups I and II) demonstrated other hormonal deficiencies (gonadotropin and adrenal insufficiencies). Among the 11 patients with persistent severe GHD (group III), 10 (91%) of the 11 subjects were shown to have multiple pituitary hormone deficits after attainment of adult height. The structure of the hypothalamo-pituitary axis differs among groups [i.e. patients who showed increased GH secretion ability in adulthood (groups I and II) vs. those who remained severely GHD (group III)]. The location of the EPPHS was significantly different among groups (P < 0.003). The EPPHS was found at the median eminence in all but one of group III patients and along the pituitary stalk (proximal stalk) in all but one of group I and II patients. The pituitary stalk was visible and described as normal (n = 1) or thin (n = 6) in all group I and II patients, whereas the pituitary stalk was not visible even after enhancement in seven of the 11 group III patients (P < 0.02). The prevalence of anterior pituitary hypoplasia and the mean height gain sd score were similar in each group. In conclusion, only 61% of patients with childhood-onset GHD and EPPHS remained severely GHD, and thus suitable for GH therapy, in adulthood. Although the pathogenesis of anterior pituitary dysfunction remains unclear in patients with ectopic neurohypophysis, isolated GHD, location of EPPHS along the stalk, and visibility of the pituitary stalk on magnetic resonance imaging findings clearly represent important markers to predict a less severe form of the disease.
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PMID:Do all patients with childhood-onset growth hormone deficiency (GHD) and ectopic neurohypophysis have persistent GHD in adulthood? 1554 1

Glucocorticoids can cause muscle atrophy, but the effect on muscle protein metabolism in humans has not been adequately studied to know whether protein synthesis, breakdown, or both are altered. We tested the effect of 6 d of oral prednisone (Pred, 0.5 mg/kg.d) on muscle protein metabolism and function. Six healthy subjects (three men/three women, 22-41 yr) completed two trials (randomized, double-blind, cross-over) with Pred and placebo. Fasting glucose, insulin, IGF-I, and glucagon were higher on Pred vs. placebo, whereas IGF-II and IGF binding protein-1 and -2 were lower. Whole-body amino acid fluxes, blood urea nitrogen, and urinary nitrogen loss were not statistically different between trials. Leg blood flow was 25% lower on Pred leading to 15-30% lower amino acid flux among the artery, vein, and muscle. However, amino acid net balance and rates of protein synthesis and breakdown were unchanged, as were synthesis rates of total mixed, mitochondrial, sarcoplasmic, and myosin heavy chain muscle proteins. Muscle mitochondrial function, muscle strength, and resting energy expenditure were also unchanged. These results demonstrate that a short-term moderate dose of prednisone affects glucose metabolism but has no effect on whole-body or leg muscle protein metabolism or muscle function.
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PMID:Effect of short-term prednisone use on blood flow, muscle protein metabolism, and function. 1557 78

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the beta cells of hypox compared with normal, age-matched rats whereas glucagon in alpha cells and somatostatin in delta cells showed increase. IGF-I, which localized to alpha cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a "low IGF-I state" affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production.
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PMID:The effect of hypophysectomy on pancreatic islet hormone and insulin-like growth factor I content and mRNA expression in rat. 1581 46

The proinflammatory cytokine interleukin-6 (IL-6) may modulate the onset and progression of complications of diabetes. As this cytokine increases after exercise, and many other exercise responses are altered by prior glycemic fluctuations, we hypothesized that prior hyperglycemia might exacerbate the IL-6 response to exercise. Twenty children with type 1 diabetes (12 boys/8 girls, age 12-15 yr) performed 29 exercise studies (30-min intermittent cycling at approximately 80% peak O2 uptake). Children were divided into four groups based on highest morning glycemic reading [blood glucose (BG) < 150, BG 151-200, BG 201-300, or BG > 300 mg/dl]. All exercise studies were performed in the late morning, after hyperglycemia had been corrected and steady-state conditions (plasma glucose < 120 mg/dl, basal insulin infusion) had been maintained for > or = 90 min. Blood samples for IL-6, growth factors, and counterregulatory hormones were drawn at pre-, end-, and 30 min postexercise time points. At all time points, circulating IL-6 was lowest in BG < 150 and progressively higher in the other three groups. The exercise-induced increment also followed a similar dose-response pattern (BG < 150, 0.6 +/- 0.2 ng/ml; BG 151-200, 1.2 +/- 0.8 ng/ml; BG 201-300, 2.1 +/- 1.1 ng/ml; BG > 300, 3.2 +/- 1.4 ng/ml). Other measured variables (growth hormone, IGF-I, glucagon, epinephrine, cortisol) were not influenced by prior hyperglycemia. Recent prior hyperglycemia markedly influenced baseline and exercise-induced levels of IL-6 in a group of peripubertal children with type 1 diabetes. While exercise is widely encouraged and indeed often considered part of diabetic management, our data underscore the necessity to completely understand all adaptive mechanisms associated with physical activity, particularly in the context of the developing diabetic child.
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PMID:Effect of prior hyperglycemia on IL-6 responses to exercise in children with type 1 diabetes. 1633 21

The high- and low-growth lines of chickens have been developed from a single founder population by divergent selection for body weight at 56 days of age for more than 40 generations. The two lines show a ninefold difference in body weight at selection age and several interesting correlated selection responses such as altered body composition and metabolic differences. We have generated a reciprocal intercross comprising >800 F2 birds. In a previous study, we reported the detection of 13 quantitative trait loci (QTLs) affecting growth. Here we report QTLs for body composition (fat deposition, muscle development), weight of internal organs, and metabolic traits (plasma concentrations of glucose, insulin, cholesterol, glucagon, triglycerides, and IGF-I). Most of the QTLs with convincing statistical support mapped in the vicinity of growth QTLs. One of the most interesting observations was that the type of reciprocal cross had highly significant effects on body weight at hatch and on plasma concentrations of glucose, cholesterol, insulin, and IGF-I, but it had no significant effect on body weight at 56 days of age. The reciprocal cross explained between 15 and 35% of the phenotypic variance for weight at hatch and for plasma concentrations of glucose and insulin. The observed pattern indicated that these effects were caused by maternal effects or by genetic differences in mitochondrial DNA.
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PMID:QTL analysis of body composition and metabolic traits in an intercross between chicken lines divergently selected for growth. 1639 Aug 76

The diagnosis of GH deficiency (GHD) in adults is established by laboratory testing in patients with an appropriate clinical history of hypothalamic pituitary disease. As the measurement of IGF-I and IGFBP-3 levels as well as the spontaneous GH secretion are not considered reliable parameters, the diagnosis of GHD in adults may be established by GH provocative tests, provided that a reproducible test with clear normative limits is available. The insulin tolerance test (ITT) is a reliable diagnostic test in adults, but is contraindicated in several clinical conditions which are often observed in adult patients with suspected GHD. The other classic GH provocative tests, except the glucagon test, have a poor diagnostic utility and should be abandoned. GHRH combined with arginine or GH secretagogues represent a potent, safe, reproducible and reliable test which should be preferable to the ITT as a first-choice diagnostic test for GHD.
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PMID:Diagnosis of adult growth hormone deficiency: still a matter of debate. 1661 Feb 49

IGF-binding proteins (IGFBPs) modulate the effects of the IGFs, major stimulators of vertebrate growth and development. In mammals, IGFBP-1 inhibits the actions of IGF-I. Rapid increases in circulating IGFBP-1 occur during catabolic states. Insulin and glucocorticoids are the primary regulators of circulating IGFBP-1 in mammals. Insulin inhibits and glucocorticoids stimulate hepatocyte IGFBP-1 gene expression and production. A 22 kDa IGFBP in salmon blood also increases during catabolic states and has recently been identified as an IGFBP-1 homolog. We examined the hormonal regulation of salmon IGFBP-1 mRNA levels and protein secretion in primary cultured salmon hepatocytes. The glucocorticoid agonist dexamethasone progressively increased hepatocyte IGFBP-1 mRNA levels (eightfold) and medium IGFBP-1 immunoreactivity over concentrations comparable with stressed circulating cortisol levels (10(-9) -10(-6) M). GH progressively reduced IGFBP-1 mRNA levels (0.3-fold) and medium IGFBP-1 immunoreactivity over physiological concentrations (5 x 10(-11)-5 x 10(-9) M). Unexpectedly, insulin slightly increased hepatocyte IGFBP-1 mRNA (1.4-fold) and did not change medium IGFBP-1 immunoreactivity over physiological concentrations and above (10(-9) -10(-6) M). Triiodothyronine had no effect on hepatocyte IGFBP-1 mRNA, whereas glucagon increased IGFBP-1 mRNA (2.2-fold) at supraphysiological concentrations (10(-6) M). This study suggests that the major inhibitory role of insulin in the regulation of liver IGFBP-1 production in mammals is not found in salmon. However, regulation of salmon liver IGFBP-1 production by other metabolic hormones is similar to what is found in mammals.
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PMID:Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin. 1708 7

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

Current guidelines for the diagnosis of adult growth hormone deficiency (GHD) state that the diagnosis must be proven biochemically by provocative testing that is done within the appropriate clinical context. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 h and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. The insulin tolerance test (ITT) is the test of choice, with severe GHD being defined by a GH peak less than 3 microg/l, the cut-off that distinguishes normal from GHD adults. The ITT is contraindicated in the presence of ischemic heart disease, seizure disorders, and in the elderly. Other tests are as reliable as the ITT, provided they are used with appropriate cut-off limits. Glucagon stimulation, a classical test, and especially new maximal tests such as GHRH in combination with arginine or GHS (i.e., GHRP-6) have well-defined cut-off limits, are reproducible, are independent of age and gender, and are able to distinguish between normal and GHD subjects. The confounding effect of overweight or obesity on the interpretation of the GH response to provocative tests needs to be considered as the somatotropic response to all stimuli is negatively correlated with body mass index. Appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults.
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PMID:Growth hormone levels in the diagnosis of growth hormone deficiency in adulthood. 1742 91

To determine the response to alteration in site and form of carbohydrate delivery to the digestive tract, in vitro rates of lipogenesis and lipolysis in mesenteric (MESA), omental (OMA), and subcutaneous (SQA) adipose depots were compared. Forty crossbred beef steers (243 +/- 2 kg of BW) were fed 161 (LI) or 214 (HI) kcal of ME/(kg of BW(0.75) x d) or they were fed LI and infused for 35 d into the rumen (R) or abomasum (A) with starch hydrolysate (SH) or into the abomasum with glucose (G). Jugular blood samples were collected, steers were slaughtered, and adipose depots were sampled and prepared for assessment of lipogenesis and lipolysis in vitro. Blood concentrations of glucagon were increased (P = 0.04) in HI-H2O compared with LI-H2O steers, whereas A-SH tended to increase (P = 0.08) circulating IGF-I relative to R-SH, and A-G tended to have elevated (P = 0.09) T3 compared with A-SH. Lipolysis, as assessed by NEFA release, was unaffected by treatment. Glycerol release by the MESA and SQA was increased or tended to be increased (P < or = 0.08) in HI-H2O compared with LI-H2O steers. In A-G compared with A-SH steers, glycerol release from OMA increased (P = 0.008) and from SQA tended to be increased (P = 0.08). Acetate incorporation into total neutral lipids (TNL) increased or tended to increase with ME intake and SH infusion (P < or = 0.09) across all depots. Rates of acetate incorporation into fatty acids (FA) also increased or tended to be increased (P < or = 0.1) by SH infusion across all depots, but only that of SQA was increased with ME intake (HI-H2O vs. LI-H2O; P = 0.02). Rates of acetate incorporation into FA and TNL in MESA were increased (P < or = 0.03) by A-SH compared with R-SH, but site of SH infusion did not affect the rates in SQA or OMA. Glucose incorporation into TNL for MESA and SQA increased or tended to be increased (P < or = 0.1) by dietary and infused energy, whereas for OMA they tended to be increased (P = 0.1) only by SH infusion. In contrast, glucose incorporation into FA was unaffected by energy supply but tended to be increased (P = 0.07) by SH in MESA and tended to be greater (P = 0.08) for A-G than A-SH in OMA. The general across-depot pattern of acetate incorporation rate into FA and TNL was SQA > OMA > MESA, whereas, for glucose incorporation, rates across depots were equivalent. These data provide evidence that the postruminal supply of energy, specifically carbohydrate, stimulates lipogenesis from acetate and glucose and is more pronounced in abdominal depots relative to the subcutaneous depot.
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PMID:Influence of abomasal carbohydrates on subcutaneous, omental, and mesenteric adipose lipogenic and lipolytic rates in growing beef steers. 1746 23


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