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)

Freshly isolated rat hepatocytes maintained as monolayers in a serum-free medium synthesize sulphated glycosaminoglycans, most of which behave as heparan sulphate and are mainly distributed into intracellular compartments. Cyclic AMP, dibutyryl cyclic AMP, glucagon, noradrenaline, prostaglandin E(1), and theophylline, all drugs and hormones known to increase intracellular cyclic AMP concentrations, decreased the incorporation of (35)SO(4) (2-) into heparan sulphate of intra-, extra- and peri-cellular pools. The inhibition mediated by dibutyryl cyclic AMP was dose-dependent and observed as early as 2h after exposure to the drug. In the presence of 1mm-dibutyryl cyclic AMP, incorporation of (35)SO(4) (2-) or [(14)C]glucosamine into heparan sulphate was decreased to 40-50%, suggesting that dibutyryl cyclic AMP interfered with the synthesis of heparan sulphate. This was further supported by pulse-chase experiments, where dibutyryl cyclic AMP had no effect on the degradation of sulphated glycosaminoglycans. Heparan sulphates synthesized and secreted into the extracellular pool in the presence of dibutyryl cyclic AMP were smaller in size, whereas the degree of sulphation and molecular size of the heparan sulphate chains released by beta-elimination from these proteoglycans were not different from control values. In the presence of 1mm-cycloheximide, (35)SO(4) (2-) incorporation was decreased to 5%. Addition of p-nitrophenyl beta-d-xyloside, an artificial acceptor of glycosaminoglycan chain synthesis, enhanced this incorporation to 18%. Dibutyryl cyclic AMP did not have any inhibitory effect on the synthesis of chains initiated on p-nitrophenyl beta-d-xylosides. Incorporation of [(3)H]serine into heparan sulphate was not affected by dibutyryl cyclic AMP, whereas the degree of substitution of serine residues with heparan sulphate chains was less in heparan sulphate synthesized in the presence of dibutyryl cyclic AMP, suggesting that cyclic AMP exerts its effect on the metabolism of sulphated glycosaminoglycans by affecting the transfer of xylose on to the protein core.
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PMID:Regulation of heparan sulphate metabolism by adenosine 3':5'-cyclic monophosphate in hepatocytes in culture. 626 52

This study investigated dietary fiber in noninsulin-dependent diabetics, the major North American diabetic population, using modest fiber increases as a strategy to promote dietary adherence. Once weekly over a 3-wk period, five lean, diet-controlled noninsulin-dependent diabetics ingested one of three isocaloric, isocarbohydrate breakfasts (337 kcal, 49 g carbohydrate), differing primarily in dietary fiber: 3 g bran (control), 17 g bran (B), or 18 g bran and fruit (BF). B and BF were higher in protein than control; BF contained more sugar than B and control. Compared to control, B reduced (p less than 0.05) plasma glucose over 180 min; BF did not. The peak blood glucose rise after BF was lower than control (p less than 0.01) whereas no effect was seen with B. B reduced xylose absorption (p less than 0.025) suggesting a reduced rate of glucose absorption; BF did not. Insulin, growth hormone, and glucagon values did not differ. This study suggests significant plasma glucose reductions with bran or bran and whole apple; other nutrient differences (higher protein in fiber meals, higher sugar with whole apple meal) might also be related. Further research is indicated to clarify these responses and extend the data to obese noninsulin-dependent diabetics.
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PMID:Effects of high fiber breakfasts on glucose metabolism in noninsulin-dependent diabetics. 633 Nov 50

The mechanisms of postprandial glucose counterregulation-those that blunt late decrements in plasma glucose, prevent hypoglycemia, and restore euglycemia-have not been fully defined. To begin to clarify these mechanisms, we measured neuroendocrine and metabolic responses to the ingestion of glucose (75 g), xylose (62.5 g), mannitol (20 g), and water in ten normal human subjects to determine for each response the magnitude, temporal relationships, and specificity for glucose ingestion. Measurements were made at 10-min intervals over 5 h. By multivariate analysis of variance, the plasma glucose (P < 0.0001), insulin (P < 0.0001), glucagon (P < 0.03), epinephrine (P < 0.0004), and growth hormone (P < 0.01) curves, as well as the blood lactate (P < 0.0001), glycerol (P < 0.001), and beta-hydroxybutyrate (P < 0.0001) curves following glucose ingestion differed significantly from those following water ingestion. However, the growth hormone curves did not differ after correction for differences at base line. In contrast, the plasma norepinephrine (P < 0.31) and cortisol (P < 0.24) curves were similar after ingestion of all four test solutions, although early and sustained increments in norepinephrine occurred after all four test solutions. Thus, among the potentially important glucose regulatory factors, only transient increments in insulin, transient decrements in glucagon, and late increments in epinephrine are specific for glucose ingestion. They do not follow ingestion of water, xylose, or mannitol. Following glucose ingestion, plasma glucose rose to peak levels of 156+/-6 mg/dl at 46+/-4 min, returned to base line at 177+/-4 min, reached nadirs of 63+/-3 mg/dl at 232+/-12 min, and rose to levels comparable to base line at 305 min, which was the final sampling point. Plasma insulin rose to peak levels of 150+/-17 muU/ml (P < 0.001) at 67+/-8 min. At the time glucose returned to base line, insulin levels (49+/-12 muU/ml) remained fourfold higher than base line (P < 0.01); thereafter they declined but never fell below base line. Plasma glucagon decreased from 95+/-14 pg/ml to nadirs of 67+/-11 pg/ml (P < 0.001) at 84+/-9 min and then rose progressively to peak levels of 114+/-17 pg/ml (P < 0.001 vs. nadirs) at 265+/-12 min. Plasma epinephrine, which was 18+/-4 pg/ml at base line, did not change initially and then rose to peak levels of 119+/-20 pg/ml (P < 0.001) at 271+/-13 min. These data indicate that the glucose counterregulatory process late after glucose ingestion is not solely due to the dissipation of insulin and that sympathetic neural norepinephrine, growth hormone, and cortisol do not play critical roles. They are consistent with, but do not establish, physiologic roles for the counterregulatory hormones-glucagon, epinephrine, or both-in that process.
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PMID:Neuroendocrine responses to glucose ingestion in man. Specificity, temporal relationships, and quantitative aspects. 640 29

Sixteen patients (aged 3.5-14.3 years) with normal jejunal mucosa, originally diagnosed as having coeliac disease at least 18 months before, were started on gluten challenge. The 'end point' of challenge was significant deterioration in jejunal mucosa morphologically and morphometrically. Studies carried out both before and after challenge included intestinal absorption of D-xylose and glucose, and release of insulin and N-terminal glucagon-like immunoreactivity (N-GLI). After gluten challenge, there were significant increases in plasma N-GLI at both 45 (P less than 0.05) and 120 minutes (P less than 0.03) after oral glucose. Significant reduction occurred in glucose absorption at 45 minutes (P less than 0.04), in one-hour D-xylose absorption (P less than 0.01) and fasting serum cholesterol (P less than 0.01). Plasma N-GLI showed significant negative correlations with D-xylose absorption (P less than 0.003) and serum cholesterol (P less than 0.004).
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PMID:Changes in N-terminal glucagon-like immunoreactivity and insulin during short-term gluten challenge in childhood coeliac disease. 702 33

The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
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PMID:Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. 865 34

Impaired growth involving both height and weight accompanying sickle cell disease (SCD) poses diagnostic and therapeutic problems. We undertook this study to test the hypothesis that this impaired growth is associated with abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF binding protein-3 (IGFBP-3) axis in 21 children with SCD and that SCD is associated with GH resistance. Nine of 21 children with SCD had a defective GH response to both clonidine and glucagon provocation (peak < 10 micrograms/L); these children differed from the 12 others in having slower linear growth velocity (GV and GVSDS), lower circulating concentrations of IGF-I and IGFBP-3, and either partial or complete empty sellae in computed tomographic scans of the hypothalamic-pituitary area. In this group of patients with SCD, it appears that defective GH secretion and consequent low IGF-I production are the major etiological factors causing the slow growth. The two groups with SCD did not differ significantly in dietary intake, body mass index (BMI), midarm circumferences, skinfold thickness, serum albumin concentration, or intestinal absorption of D-xylose. A single injection of GH produced a smaller increase in circulating IGF-I in children with SCD with or without defective GH secretion versus 10 age-matched children with idiopathic short stature (ISS) and 11 children with isolated GH deficiency (GHD), suggesting partial GH resistance in the SCD group. The presence of defective GH secretion, decreased IGF-I synthesis, and partial resistance to GH in short children with SCD suggests that treatment with IGF-I may be superior to GH therapy for improving growth.
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PMID:Growth hormone secretion and circulating insulin-like growth factor-I (IGF-I) and IGF binding protein-3 concentrations in children with sickle cell disease. 936 79

The present experiments sought to determine whether glucagon concentrations mimicking those observed in people with diabetes mellitus alter postprandial carbohydrate metabolism in nondiabetic humans. We measured the gastric emptying of solids and liquids, the systemic rate of appearance of ingested glucose, and endogenous glucose production either when postprandial suppression of glucagon was prevented by infusing glucagon at a rate of 0.65 ng/kg/min, when postprandial glucagon concentrations were elevated by infusing glucagon at a rate of 3.0 ng/kg/min, or when postprandial suppression of glucagon was permitted by infusion of saline. Despite marked differences in glucagon concentrations, postprandial glucose and insulin concentrations did not differ on any occasion. Although gastric emptying of liquids and solids was comparable on all three occasions, the high-dose, but not the low-dose, glucagon infusion caused a slight delay in the systemic appearance of ingested glucose and a significant decrease (P < .01) in postprandial D-xylose concentrations, suggesting a delay in carbohydrate absorption. However, this was offset by an increase (P < .05) in endogenous glucose production, resulting in no difference in postprandial glucose appearance. We conclude that in the absence of insulin deficiency, neither a lack of suppression of glucagon nor an elevation of glucagon to levels encountered in uncontrolled diabetes mellitus cause postprandial hyperglycemia in nondiabetic humans.
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PMID:Effects of glucagon on postprandial carbohydrate metabolism in nondiabetic humans. 944 Apr 70

To determine whether treatment with a potent protease-resistant analog of human glucagon-like peptide 2 (GLP-2) might augment the adaptive response to massive intestinal resection, rats were divided into resected, which had 75% of the midjejunoileum removed, sham-resected, and nonsurgical groups. Within each group, animals were assigned to 21 days of treatment with the drug (0.1 micrograms/g of the GLP-2 analog in phosphate-buffered saline) or vehicle alone subcutaneously twice daily. Food intake; weight gain; jejunal and ileal diameters, total and mucosal wet weights per centimeter, crypt depths, and villus heights; mucosal sucrase activity, milligrams of protein per centimeter, and micrograms of DNA per centimeter; and D-xylose absorption were measured. There was a significant increase in diameter, total and mucosal wet weights per centimeter, crypt-villus height, sucrase activity, milligrams of protein per centimeter and micrograms of DNA per centimeter in both the jejunum and ileum in response to resection and a significant additive response to the GLP-2 analog in the jejunum but not in the ileum. The ratio of milligrams of protein per centimeter to micrograms of DNA per centimeter of mucosa was not different among groups, consistent with hyperplasia. D-Xylose absorption was significantly reduced in response to resection; however, the GLP-2 analog enhanced the absorptive capacity in control animals and restored the absorptive capacity in resected animals. Thus the GLP-2 analog induces mucosal hyperplasia and enhances the rate and magnitude of the proximal intestinal adaptive response to massive resection.
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PMID:GLP-2 augments the adaptive response to massive intestinal resection in rat. 981 19

Colostrum intake is important for health and postnatal development of neonatal calves. We studied the effects of enhanced first colostrum feeding on growth, health status, and metabolic and endocrine traits in calves during their 1st wk of life. Calves of group CL (GrCL; n = 7) were fed colostrum of milkings 1 to 6 twice daily during the first 3 d of life, followed by milk replacer (MR) up to d 7. Calves of group CH (GrCH; n = 7) were fed colostrum of the first milking during the first 3 d and then colostrum (of the first milking) twice daily, which on d 4, 5, 6, and 7 was diluted with 25, 50, 75, and 75 parts of MR, respectively. Pre- and postprandial blood samples were taken on d 1, 2, 3, and 7 for the determination of various metabolic and endocrine traits, and on d 5 intestinal absorption capacity was measured using the xylose absorption test. Rectal temperatures and fecal scores were higher (P < .05) in GrCH than in GrCL. Plasma concentrations of total protein and albumin were higher (P < .05) on d 7, IgG on d 2 and 3, and urea on d 2, 3, and 7 in GrCH than in GrCL. Plasma concentrations of triglycerides were higher (P < .05) on d 2 and of phospholipids and cholesterol were higher (P < .01) on d 7 in GrCH than in GrCL. Plasma insulin and glucagon concentrations were higher (P < .05) in GrCH than in GrCL, whereas prolactin and growth hormone concentrations were higher (P < .05) in GrCL than in GrCH. Enhanced colostrum intake had no effects on xylose absorption on d 5. Higher plasma protein, urea, and lipid concentrations in GrCH partly mirrored higher protein and fat intake but additionally pointed to higher protein synthesis and lipid turnover.
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PMID:Influence of feeding different amounts of first colostrum on metabolic, endocrine, and health status and on growth performance in neonatal calves. 1078 79

Colostrum provides high amounts of nutrients and non-nutrient substances to neonates. To study differences between effects of nutritional and non-nutritional components on growth, health status and metabolic and endocrine traits, a formula was created based on bovine milk components which contained similar amounts of nutrients as bovine colostrum during the first 3 days of lactation, but only trace amounts of growth factors (such as insulin-like growth factor I) or hormones (such as insulin) in whey. Calves were fed either pooled colostrum of milkings 1 to 6, obtained during the first 3 days of lactation (GrC, n = 7) or a formula in the same amounts as colostrum (GrF, n = 7) for the first 3 days, followed by a milk replacer up to day 7. Pre- and postprandial blood samples were taken on days 1, 2, 3 and 7 for the determination of metabolic and endocrine traits and on day 5 we measured intestinal absorptive capacity by testing xylose absorption. Plasma concentrations of total protein and immunoglobulin G and gamma-glutamyltransferase activity were lower (p < 0.05), whereas albumin and urea concentrations were higher (p < 0.05) in GrF than GrC during the first week of life. Plasma glucose concentrations were variably affected. Plasma triglyceride, phospholipid and cholesterol concentrations were higher (p < 0.05) in GrC than GrF on days 3 and 7. Insulin and growth hormone concentrations were higher (p < 0.05) in GrC than GrF on days 2 and 3 and on days 1 and 2, respectively, and glucagon concentrations were higher (p < 0.05) in GrC than GrF on day 1 and higher (p < 0.05) in GrF than GrC on day 3. Cortisol concentrations were higher (p < 0.05) on days 2 and 3 in GrF than GrC. Plasma xylose concentrations rose more markedly (p < 0.05) in GrC than GrF. In conclusion, feeding only trace amounts of bioactive substances appears to impair intestinal absorptive capacity and protein and fat metabolism and exert effects on endocrine systems in neonatal calves.
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PMID:Effects of feeding colostrum and a formula with nutrient contents as colostrum on metabolic and endocrine traits in neonatal calves. 1087 23


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