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)

Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.
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PMID:Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity. 1068 87

Auxological and endocrine data from 12 prepubertal children (3 males, 9 females) with Noonan syndrome (NS) were compared with those of 15 children with constitutional short stature (CSS), 20 children with partial GH deficiency (GHD), and 6 children with Turner syndrome (TS). Four children with NS were treated with human growth hormone (hGH) (n = 4) (25 units/m2 week, divided on daily s.c. doses). In children with NS, the peak serum GH response to clonidine (5.4 +/- 2.7 ug/L) and glucagon (7.4 +/- 3.4 ug/L) were significantly lower than those for children with CSS (14.8 +/- 3.4 and 12.8 +/- 2.8 ug/L respectively). Nine out of the 12 (75%) children with NS did not mount normal GH peak (10 ug/L or more) after provocation. The 12-h integrated GH secretion in the 3 children with NS who had normal GH response to provocation (2.7 +/- 0.7 ug/L) was markedly lower compared to that for children with CSS (6.7 +/- 1.2 ug/L). The serum insulin-like growth factor-1 (IGF-I) concentrations were lower in children with NS (67 +/- 32 ng/ml) vs CSS (165 +/- 35 ng/ml), but not different from those for GHD children (59 +/- 33 ng/ml). In 4 children with NS, hGH therapy for a year increased height growth velocity from 4.1 +/- 0.3 cm/yr to 7.4 +/- 0.6 cm/yr and height standard deviation score (Ht SDS) from -2.2 +/- 0.6 to -1.45 +/- 0.3. This growth acceleration was accompanied by an increase in IGF-I concentration (from 52 +/- 21 ng/ml to 89 +/- 25 ng/ml). In summary, these results prove a defect of the GH secretion in children with NS and suggest that GH therapy has an important role in the management of their short stature.
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PMID:Defective growth hormone (GH) secretion and short-term treatment in Noonan syndrome. 1077 31

The effect of feed intake level (.6, 1.0, and 1.6 x maintenance energy and protein requirements, M) on splanchnic (portal-drained viscera [PDV] plus liver) metabolism was evaluated in six multicatheterized beef steers (398 +/- 27 kg), using a double 3 x 3 Latin square design. On the last day of each 21-d experimental period, six hourly blood samples were collected from arterial, portal, and hepatic vessels. Due to catheter patency, PDV fluxes were measured on five steers, and liver and splanchnic fluxes on four steers. Increasing intake elevated (P < .01) splanchnic release of total (T) amino acids (AA), through increases (P < .01) in PDV release of both essential (E) and nonessential (NE) AA, in spite of a tendency (P < .20) for increased liver removal of NEAA. The PDV release of AA N represented 27 and 51% of digested N for 1.0 and 1.6 x M, respectively. At 1.0 and 1.6 x M, the liver removed 34% of total AA released by the PDV. For individual AA, portal flux of most EAA increased (P < .05) with feed intake, and the increase (P < .10) in splanchnic flux was accompanied by increased arterial concentration for all EAA except histidine, lysine, and methionine. This suggests that these might be limiting AA for this diet. On a net basis, most individual NEAA were released by the PDV except glutamate and glutamine, which were removed by the digestive tract. There was a net removal of NEAA by the liver, except for aspartate and especially glutamate, which were released. Ammonia release by the PDV tended (P < .20) to increase with intake and represented 69, 53, and 45% of digested N at .6, 1.0, and 1.6 x M, respectively. Urea removed by the PDV, unaffected by intake, represented 32, 33, and 21% of the digested N. Arterial glucose concentration increased linearly (P < .01) with greater intake, whereas net liver and splanchnic glucose release increased in a quadratic (P < .05) manner. Net PDV glucose release represented 26% of net glucose hepatic release at 1.6 x M. Intake elevated (P < .10) both insulin and glucagon arterial concentrations, resulting from a larger increment of portal release (P < .01) than hepatic removal (P < .05). Intake-based variations in IGF-I and NEFA arterial concentrations (P < .05) were not related to changes in splanchnic metabolism. These results clearly show the crucial role of the splanchnic tissues in regulating the profile and quantity of AA and concentrations of glucose and pancreatic hormones reaching peripheral tissues.
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PMID:The effect of feed intake level on splanchnic metabolism in growing beef steers. 1078 2

We report the case of a 7-year-old patient of short stature who had normal GH secretion, but a very low serum IGF-I level. On admittance, his height and weight were 102.2 cm (-3.8S.D.) and 15.7 kg (-1.8S.D.), respectively. His bone age was 2 years and 8 months. The serum GH responses to insulin, glucagon and L-dopa were all normal. GH secretion during sleep was also normal, but the serum IGF-I level was very low (29 ng/ml). The serum IGF-I level was greatly increased by the administration of GH. No mutation was detected in the GH-1 gene. His height velocity was noticeably improved by GH treatment.
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PMID:A patient of short stature with normal GH secretion, but a low serum IGF-I level. 1089 Feb

High vascular morbidity and mortality is associated with acromegaly. The aim of the present study was to assess the effects of octreotide therapy on several known cardiovascular risk factors and to correlate them with octreotide-induced hormonal changes. Lipid levels, LDL particle size distribution as evaluated by single vertical spin density gradient ultracentrifugation, apolipoproteins AI and B, lipoprotein (a) [Lp(a)] concentrations and apo(a) phenotypes were evaluated in 20 non-diabetic acromegalic patients (6 M, 14 F), with normal thyroid, adrenal and gonadal function, aged 29-66 years. Normal subjects (20), matched for age, sex and BMI served as control for lipid variables. Acromegalic patients were characterized by lower HDL cholesterol (and apoA-I) and by higher Lp(a) concentrations in comparison to controls. Treatment with octreotide (100 microg t.i.d. for 3 months) led to: an increase in HDL cholesterol (median: + 22%), a decrease in LDL cholesterol (-14%) and a decrease of the Lp(a) levels (all phenotypes) (-28%). The expected decreases of IGF-I levels (median: -48%) and 7-h AUC of GH (-50%), insulin (-40%) and glucagon (-20%) were observed. Only Lp(a) modifications showed a correlation with GH modifications. The study of LDL physical properties showed that acromegalic patients had smaller and/or more dense LDL particles, in comparison with normal controls (relative flotation rate, Rf: 0.40 +/- 0.03 versus 0.42 +/- 0.02 P < 0q05), an alteration that might contribute to the high vascular risk of acromegalic patients. However, the LDL subfraction distribution remained unmodified during octreotide therapy (Rf 0.39 +/- 0.03). In conclusion, this study shows that in acromegalic patients octreotide treatment is indeed associated with an amelioration of some lipoprotein parameters, i.e. LDL, HDL, and Lp(a) concentrations. However, this treatment has no effect on the small and/or dense LDL particles present in these patients.
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PMID:LDL physical properties, lipoprotein and Lp(a) levels in acromegalic patients. Effects of octreotide therapy. Italian Multicenter Octreotide Study Group. 1092 34

To determine whether the hormonal regulation of IGF-I production differs between granulosa and thecal cells in cattle, granulosa and thecal cells from bovine follicles were collected, cultured for 2 d in medium containing 10% fetal calf serum, washed, and then treated for an additional 24 h in serum-free medium with various hormones. In Exp. 1, granulosa cells were treated with 0 or 100 ng/mL of insulin and(or) 50 ng/mL of follicle-stimulating hormone (FSH), insulin plus 10 ng/mL of epidermal growth factor, or insulin plus 10 ng/mL of basic fibroblast growth factor. In Exp. 2, thecal cells were treated as described in Exp. 1 except that 100 ng/mL of luteinizing hormone (LH) was used instead of 50 ng/mL of FSH. In Exp. 3, granulosa and thecal cells were treated with 0 or 30 ng/mL of cortisol with or without 100 ng/mL of insulin, 300 pg/mL of glucagon, or glucagon plus insulin. In Exp. 4, granulosa and thecal cells were treated with 0 or 300 ng/mL of estradiol with or without 100 ng/mL of insulin and(or) 100 ng/mL of LH. At the end of treatment, medium was collected, concentrated with Centricon-3 concentrators, and assayed for IGF-I by radioimmunoassay. Cell numbers were determined by Coulter counting at the end of culture. Thecal cells produced low amounts of IGFI (0.48 +/- 0.04, 0.63 +/- 0.03, and 0.82 +/- 0.03 ng per 100,000 cells per 24 h in Exp. 2, 3, and 4, respectively), and this production was not influenced (P > 0.05) by the various treatments. In contrast, IGF-I production by granulosa cells (2.0 to 6.2 ng per 100,000 cells per 24 h) was influenced by treatment in Exp. 1, 3, and 4 and was greater than IGF-I production by thecal cells (Exp. 2, 3, and 4). Alone, insulin, FSH, LH, and cortisol (but not estradiol) each decreased (P < 0.05) granulosa-cell IGF-I production by 20 to 57%; combined treatments of insulin plus FSH or insulin plus cortisol decreased IGF-I production to levels seen with insulin alone. Glucagon had no effect (P > 0.10) on IGF-I production in the absence or presence of insulin. In the presence of insulin, epidermal growth factor, basic fibroblast growth factor, and estradiol decreased (P < 0.05) IGF-I production below that observed for insulin alone. These results indicate that, during follicular development in cattle, changes in intrafollicular levels of IGF-I may be due to hormonally-induced changes in granulosa-cell, but not thecal-cell, IGF-I production.
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PMID:Production of insulin-like growth factor-I by granulosa cells but not thecal cells is hormonally responsive in cattle. 1106 17

Veal calves fed by bucket often develop postprandial insulin resistance, hyperglycemia, and glucosuria during fattening. Automatic feeding systems allow feed intake for 24 h, and small ingested portions are expected to decrease postprandial glucose loads. We have studied metabolic and endocrine traits in calves that were either 1) fed identical daily amounts of whole milk plus milk replacer by a computer-programmed automatic feeder (> or =6 portions from 0800 to 2400 h) (GrA) or 2) fed by bucket at 0800 and 1630 h (GrB). Calves started at a body weight of 118 kg, and the experiment lasted for 3 wk. During wk 3, lactose was supplemented to stress postabsorptive glucose homeostasis. Feed intake and average daily gains in GrA and GrB were similar. Plasma concentrations during an 8-h period of glucose (in part), lactate, urea, and somatostatin (in wk 3), and of glucagon and insulin (wk 2 and 3) were smaller in GrA than in GrB, whereas growth hormone, insulin-like growth factor I, insulin-like growth factor binding protein-1 (wk 2), and prolactin concentrations (wk 2 and 3) were higher. Lactose supplementation in wk 3 enhanced transient postprandial hyperglycemia and hyperinsulinemia. Thus, there were marked metabolic and endocrine differences when calves sucked their feed in six or more portions during a 16-h period from an automatic feeder compared with twice daily drinking from a bucket. Ingestion of small portions by calves avoided marked hyperglycemia and lactate increments, and lower plasma urea concentrations mirrored enhanced nitrogen utilization, possibly mediated by the altered growth hormone, IGF-I and insulin status.
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PMID:Postprandial metabolism and endocrine status in veal calves fed at different frequencies. 1110 67

At supraphysiological levels, IGF-I bypasses some forms of insulin resistance and has been proposed as a therapeutic agent in the treatment of diabetes. Unfortunately, side effects of high-dose IGF-I (100-250 microg/kg) have precluded its clinical use. Low-dose IGF-I (40-80 microg/kg), however, shows minimal side effects but has not been systematically evaluated. In our previous study under conditions of declining glucose, low-dose IGF-I infusion was more effective in stimulating glucose utilization, but less effective in suppressing glucose production and lipolysis than low-dose insulin. However, under conditions of hyperglycemia, we could not observe any differential effects between high-dose infusions of IGF-I and insulin. To determine whether the differential effects of IGF-I and insulin are dose-related or related to the prevailing glucose level, 3 h glucose clamps were performed in the same animal model as in the previous studies, i.e. the moderately hyperglycemic (175 mg/dl) insulin-infused depancreatized dog, with additional infusions of low-dose IGF-I (67.8 microg/kg, i.e. 29.1 microg/kg bolus plus 0.215 microg/kg( )per min infusion; n=5) or insulin 49.5 mU/kg (9 mU/kg bolus plus 0.45 mU/kg per min; n=7). As in the previous study under conditions of declining glucose, low-dose IGF-I had significant metabolic effects in vivo, in our model of complete absence of endogenous insulin secretion. Glucose production was similarly suppressed with both IGF-I and insulin, by 54+/-3 and 56+/-2% s.e. (P=NS) respectively. Glucose utilization was stimulated to the same extent (IGF-I 5.2+/-0.2, insulin 5.5+/-0.3 mg/kg per min, P=NS). Glucagon, free fatty acid, glycerol, alanine and beta-hydroxybutyrate, were suppressed, while lactate and pyruvate levels were raised, similarly with IGF-I and insulin. We conclude that: (i) differential effects of IGF-I and insulin may be masked under hyperglycemic conditions, independent of the hormone dose; (ii) low-dose IGF-I has no selective advantage over additional insulin in suppressing glucose production and lipolysis, nor in stimulating glucose utilization during hyperglycemia and subbasal insulin infusion when insulin secretion is absent, as in type 1 diabetes mellitus.
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PMID:Low-dose IGF-I has no selective advantage over insulin in regulating glucose metabolism in hyperglycemic depancreatized dogs. 1113 69

The metabolic response to fasting involves a series of hormonal and metabolic adaptations leading to protein conservation. An increase in the serum level of growth hormone (GH) during fasting has been well substantiated. The present study was designed to test the hypothesis that GH may be a principal mediator of protein conservation during fasting and to assess the underlying mechanisms. Eight normal subjects were examined on four occasions: 1) in the basal postabsorptive state (basal), 2) after 40 h of fasting (fast), 3) after 40 h of fasting with somatostatin suppression of GH (fast-GH), and 4) after 40 h of fasting with suppression of GH and exogenous GH replacement (fast+GH). The two somatostatin experiments were identical in terms of hormone replacement (except for GH), meaning that somatostatin, insulin, glucagon and GH were administered for 28 h; during the last 4 h, substrate metabolism was investigated. Compared with the GH administration protocol, IGF-I and free IGF-I decreased 35 and 70%, respectively, during fasting without GH. Urinary urea excretion and serum urea increased when participants fasted without GH (urea excretion: basal 392 +/- 44, fast 440 +/- 32, fast-GH 609 +/- 76, and fast+GH 408 +/- 36 mmol/24 h, P < 0.05; serum urea: basal 4.6 +/- 0.1, fast 6.2 +/- 0.1, fast-GH 7.0 +/- 0.2, and fast+GH 4.3 +/- 0.2 mmol/1, P < 0.01). There was a net release of phenylalanine across the forearm, and the negative phenylalanine balance was higher during fasting with GH suppression (balance: basal 9 +/- 3, fast 15 +/- 6, fast-GH 17 +/- 4, and fast+GH 11 +/- 5 nmol/min, P < 0.05). Muscle-protein breakdown was increased among participants who fasted without GH (phenylalanine rate of appearance: basal 17 +/- 4, fast 26 +/- 9, fast-GH 33 +/- 7, fast+GH 25 +/- 6 nmol/min, P < 0.05). Levels of free fatty acids and oxidation of lipid decreased during fasting without GH (P < 0.01). In summary, we find that suppression of GH during fasting leads to a 50% increase in urea-nitrogen excretion, together with an increased net release and appearance rate of phenylalanine across the forearm. These results demonstrate that GH-possibly by maintenance of circulating concentrations of free IGF-I--is a decisive component of protein conservation during fasting and provide evidence that the underlying mechanism involves a decrease in muscle protein breakdown.
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PMID:The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown. 1114 1

The role of GH insufficiency in the pathogenesis of short stature in Noonan syndrome is unclear. Cross-sectional study. Seventeen patients with Noonan syndrome (13 boys, 4 girls; aged 4.8-13.3 (mean 9.2) years) and short stature before start of GH treatment. Spontaneous 12-h overnight GH secretion by continuous sampling analysed using Pulsar, plasma IGF-I and IGFBP-3 levels, and 24-h urinary GH excretion were measured at start of GH treatment. A glucagon stimulation test was performed. Height and height velocity were monitored before and after 1 year of GH treatment. IGF-I and IGFBP-3 were remeasured after 1 year of GH treatment. Nine of the 17 children had a mean overnight GH concentration below the lower limit of the normal range. In six of the 17 patients, overnight GH profiles showed high trough GH concentrations. Glucagon stimulation tests were normal in 16 of the 17 patients. Mean IGF-I level was below normal (-0.4 SD). None of the parameters regarding GH secretion obtained from the overnight profile or provocative test was related to height or height velocity, nor to first year response to GH treatment. IGF-I and IGFBP-3 did not correlate with any of the GH secretion data. IGF-I and IGFBP-3 were related to height and height velocity at the start of GH treatment (r = 0.53 (P < 0.01) and r = 0.61 (P < 0.03) respectively). Rises in IGF-I and IGFBP-3 under GH treatment were related to the increment in height velocity (r = 0.70 (P < 0.01) and r = 0.71 (P < 0.02) respectively). Abnormalities in GH secretion are frequent in patients with Noonan syndrome and short stature. These abnormalities were not related to auxology at start of or response to GH treatment. Clinically GH insufficiency is not important in Noonan syndrome and monitoring spontaneous GH secretion is not necessary before the start of GH treatment.
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PMID:Growth hormone (GH) secretion in children with Noonan syndrome: frequently abnormal without consequences for growth or response to GH treatment. 1116 26


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