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)

Islets isolated from the dorsal and ventral areas of the rat pancreas (dorsal and ventral islets) were found to have similar insulin and total protein contents. Dorsal islets, however, contained more glucagon and somatostatin than ventral islets. Dorsal islets secreted significantly more insulin in the presence of 16.7 mM glucose and 20 mM D-glyceraldehyde than did ventral islets. Leucine-induced (20 mM) insulin secretion from the two types of islet was similar. The amounts of somatostatin secreted by the two types of islet were similar both in the presence of 16.7 mM glucose and in the presence of 20 mM D-glyceraldehyde. By contrast, more glucagon was secreted by dorsal than by ventral islets in the presence of 16.7 mM glucose. It was found that the difference in glucagon secretion between the dorsal and ventral islets in the presence of 16.7 mM glucose may be an explanation for the difference in the rate of insulin secretion under these conditions. The results suggest that glucagon may exert an important intraislet control on insulin secretion.
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PMID:Ventral and dorsal areas of rat pancreas: islet hormone content and secretion. 611 29

Investigation of the subcellular and molecular components of insulin secretion has been made difficult by the small quantities of material available. The recent development of a transplantable rat islet cell tumour of high insulin content and state of differentiation suggested a system more amenable to analysis. To validate the tumour as a model of secretion we have studied its release of insulin. In acute experiments in vitro immunoreactive insulin release was increased by leucine, glucagon, theophylline and dibutyryl cyclic AMP, though not by glucose. Leucine (20 mmol/l) plus theophylline (5 mmol/l) caused an abrupt, sustained and rapidly reversible stimulation of two- to fivefold. The response was inhibited by antagonists of cellular oxidative phosphorylation (cyanide, 2,4-dinitrophenol, antimycin A), calcium flux (EGTA, verapamil, Mg2+), calmodulin (trifluoperazine), microtubules (vinblastine, colchicine) and by adrenaline and somatostatin. These findings suggest that the tumour secretes insulin by an exocytotic mechanism similar to that of normal islet tissue.
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PMID:Insulin secretion by a transplantable rat islet cell tumour. 611 93

To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 muU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and alpha-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. l,4,5,[(3)H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute). Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2+/-0.2 mumol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P < 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24+/-0.03 mumol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (-10+/-1 mumol/liter) and KIC (-12+/-2 mumol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128+/-8 to 82+/-7 mumol/liter, P < 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P < 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.
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PMID:Role of insulin in the regulation of leucine kinetics in the conscious dog. 612 47

A clonal hamster beta cell line (HIT) was established by simian virus 40 transformation of Syrian hamster pancreatic islet cells. Cytoplasmic insulin was detected in all cells by indirect fluorescent antibody staining, and membrane-bound secretory granules were observed ultrastructurally. Acidified-ethanol extracts of HIT cell cultures contained hamster insulin as determined by radioimmunoassay, radioreceptor assay, and bioassay. One subclone at passage 39 contained 2.6 micrograms of insulin per mg of cell protein. [3H]Leucine-labeled HIT insulin and proinsulin were identical to islet-derived proteins when compared by NaDodSO4/polyacrylamide gel electrophoresis of immunoprecipitates. HIT cell insulin secretion was stimulated by glucose, glucagon, and 3-isobutyl-1-methylxanthine. Insulin secretion at optimal glucose concentration (7.5 mM) was 2.4 milliunits per 10(6) cells per hr. Somatostatin and dexamethasone markedly inhibited HIT insulin secretion. The HIT cell line represents a unique in vitro system for studying beta cell metabolism and insulin biosynthesis.
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PMID:Insulin synthesis in a clonal cell line of simian virus 40-transformed hamster pancreatic beta cells. 627 Jun 73

The present studies were undertaken to assess the effects of excess cortisol on amino acid exchange in the conscious dog. Three groups of 18-hr fasted dogs with catheters chronically implanted in the femoral artery were studied: Group I (n = 6) received saline; Groups II and III (n = 5, each) received ACTH intravenously (1 U/min) for 7 hr; in addition, Group III received ACTH, 500 U/day intramuscularly for 4 days. Leucine rates of appearance (Ra) and clearance were measured using a constant infusion of L-4,5-[3H]leucine. ACTH treatment resulted in a 9-fold increase in plasma cortisol in Groups II and III (from 2 +/- 1 to 18 +/- 1 and 17 +/- 2 micrograms/dl, in II and III, respectively P less than 0.001), with no effect on either plasma insulin or glucagon. Plasma leucine (mmole/liter) increased from 118 +/- 6 (I) to 153 +/- 6 (II, P less than 0.005) to 275 +/- 35 (III, P less than 0.001). Leucine Ra (micromoles/kilogram/minute) did not change in II, but rose by 39% (P less than 0.005) in III. Clearance (milliliters/kilogram/minute) dropped from 25 +/- 2 (I) to 18 +/- 2 (II, P less than 0.005), to 15 +/- 2 (III, P less than 0.001). It is concluded that acute elevations of cortisol increased plasma leucine only by inhibiting its rate of disposal, whereas chronic elevations had a dual effect; they inhibited leucine disposal and increased its entry into the plasma compartment, suggesting an inhibition of protein synthesis and stimulation of protein breakdown.
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PMID:The effect of acute and chronic glucocorticoid excess on leucine kinetics and protein turnover in vivo. 631 45

Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 micrograms/kg X min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10 +/- 1 to 42 +/- 4 micrograms/dl) during cortisol infusion and decreased (14 +/- 2 to 10 +/- 2 micrograms/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P less than 0.05) during cortisol infusion (120 +/- 1 to 203 +/- 21 microM) than saline (118 +/- 8 to 154 +/- 4 microM) as a result of a greater (P less than 0.01) increase in its Ra during cortisol infusion (1.47 +/- 0.08 to 1.81 +/- 0.08 mumol/kg X min for cortisol vs. 1.50 +/- 0.08 to 1.57 +/- 0.09 mumol/kg X min). Leucine nitrogen Ra increased (P less than 0.01) from 2.35 +/- 0.12 to 3.46 +/- 0.24 mumol/kg X min, but less so (P less than 0.05) during saline infusion (2.43 +/- 0.17 to 2.84 +/- 0.15 mumol/kg X min, P less than 0.01). Alanine Ra increased (P less than 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P less than 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
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PMID:Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range. 636 73

The relative contribution of hyperglucagonemia to the mechanisms of nitrogen loss during catabolic states has not been clearly established. The present study examines the independent effect of physiologic elevations of plasma glucagon on whole-body protein kinetics, as well as on net amino acid balance across the liver and gastrointestinal tract tissues, in conscious 18-hour-fasted dogs (n = 7). Each study consisted of a 120-minute equilibration period, a 30-minute basal period, and a 150-minute experimental period. Leucine kinetics were measured using L-[1-14C]leucine. Pancreatic hormones were maintained by infusing intravenous somatostatin (0.8 micrograms/kg.min), intraportal insulin (275 microU/kg.min), and intraportal glucagon (0.65 ng/kg.min basally and 2.5 experimentally). Dextrose was infused to maintain plasma glucose constant (14.1 +/- 0.3 mumol/L), thereby providing a consistent metabolic steady state for the study of protein and amino acid metabolism. In the experimental period, plasma glucagon was fourfold basal levels (112 +/- 10 v 32 +/- 6 pg/mL), whereas plasma insulin remained stable (mean, 10 +/- 1 microU/mL). Hepatic glucose production was increased 30%, but leucine rates of appearance ([Ra] proteolysis), oxidative disappearance (Rd), and nonoxidative Rd (protein synthesis) were not altered during the experimental period. Furthermore, the net release of amino acids by the gastrointestinal tract was not increased by glucagon. However, uptake and extraction of amino acids by the liver were increased, resulting in a 17% decrease in total plasma amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of glucagon in the control of protein and amino acid metabolism in vivo. 799 Jul 4

The anabolic actions of GH are well known, although specific tissue responses and the mechanism of nitrogen conservation are less well understood. This study was designed to examine the acute metabolic effects of GH on whole body and regional protein metabolism, using an experimental protocol which controlled for confounding perturbations in other hormones by a simultaneous infusion of somatostatin. Control subjects received replacement doses of insulin, glucagon, and GH for the entire 7-h study period, whereas GH subjects received an identical protocol, except for an increased dose of GH sufficient to increase serum concentrations into the high-physiological range (12-20 ng/mL) for the final 3.5 h of the study (P < 0.001). Thirteen young, healthy male subjects were studied in the postabsorptive period; five served as control subjects and eight as treatment (GH) subjects. Each received continuous iv infusions of somatostatin, L-[13-C]leucine, and L-[2H5]phenylalanine throughout the study. Femoral arterial and venous sampling allowed for simultaneous measurements across the leg and in the whole body. C-Peptide levels were suppressed throughout the infusion; insulin, glucagon, insulin-like growth factor I, cortisol, epinephrine, norepinephrine, and glucose concentrations were not different between groups. Glycerol concentrations increased 3-fold in GH subjects during the final 3.5-h period (P = 0.04). Concentrations of several amino acids declined through the study, but no differences were observed between treatment groups. Leucine oxidation was reduced in GH compared to control subjects (P = 0.04). No changes in CO2 production or whole body leucine or phenylalanine flux were observed, whereas nonoxidative disposal of leucine was marginally higher in GH compared to control subjects (P = 0.07). By contrast, rates of appearance and disappearance of both leucine and phenylalanine across the leg all were relatively lower in GH compared to control subjects; leucine balance across the leg was reduced by GH (P = 0.03), whereas phenylalanine balance was not influenced by GH. Our data thus demonstrate an acute stimulatory effect of GH on lipolysis, a decrease in leucine oxidation, and no stimulation of muscle protein synthesis in spite of enhanced protein synthesis in nonmuscle tissue.
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PMID:Acute growth hormone effects on amino acid and lipid metabolism. 817 57

We examined the role of central neuroglucopenia, induced by intracerebroventricular (i.c.v.) administration of 2-deoxyglucose (2-DG), on glucose and amino acid kinetics in conscious dogs. Group 1 received i.c.v. 2-DG at 2.5 mg.kg-1 x min-1 for 15 min. Group 2 received an equal intravenous (i.v.) amount of 2-DG. In the i.c.v. group, plasma glucose levels rose from 106 +/- 4 mg/dl to a peak of 204 +/- 12 mg/dl by 90 min. Blood lactate increased from 689 +/- 1 to 2,812 +/- 5 mumol/l and blood alanine not change from basal (256 +/- 41 mumol/l). The rate of hepatic glucose production, determined isotopically, was increased 2-fold over basal (P < 0.01). Significant increases (P < 0.001) over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon and cortisol. Leucine rate of appearance (Ra) showed a 30% decrease from basal to 2.4 +/- 0.05 mumol.kg-1 x min-1 (P < 0.01). In group 2 plasma glucose levels were not altered but plasma cortisol and glucagon showed a modest transient increase above basal (P < 0.05). No significant changes were noted in amino acid kinetics. These findings suggest that periventricular neuroglucopenia, in the absence of peripheral glucose deprivation, is accompanied by hyperglycemia secondary to enhanced hepatic glucose production with decreased glucose utilization and by increased hepatic uptake of gluconeogenic precursors. These, however, were not accompanied by increased whole body proteolysis as was previously seen with generalized glucopenia resulting from insulin-induced hypoglycemia.
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PMID:Hormonal and metabolic effects of neuroglucopenia. 834 33

The catabolic state of poorly controlled type 1 diabetes has largely been attributed to insulin deficiency. However, the role of hyperglucagonemia, which occurs concomitantly with insulin deficiency, has not been fully investigated. We studied the effects of hyperglucagonemia during insulin deprivation on energy expenditure (using indirect calorimetry) and protein metabolism (using L-[1-(13)C,15N]leucine and L-[1-(13)C]leucine as tracers) in 12 type 1 diabetic subjects. Five protocols were used: insulin treatment, insulin deprivation, insulin deprivation with suppression of endogenous glucagon with somatostatin (SRIH) and growth hormone replacement, insulin deprivation with endogenous glucagon suppression with SRIH (no growth hormone replacement), and insulin deprivation with SRIH and a high level of glucagon replacement (no growth hormone replacement). It was observed that leucine oxidation and the resting metabolic rate (RMR) were significantly lower during insulin treatment and insulin deprivation with concomitant SRIH infusion (lowering glucagon) than during insulin deprivation alone. Replacement of glucagon at a high level during SRIH infusion in the insulin-deprived state increased leucine oxidation and the RMR. Hyperglucagonemia was also associated with a trend for decreased protein synthesis. Hyperglucagonemia did not affect leucine transamination. Insulin replacement decreased leucine flux and oxidation. Leucine oxidation (R2 = 0.79) and the RMR (R2 = 0.81) were seen, by multiple regression analysis, to correlate with glucagon levels and not with other hormones. We conclude that while insulin deficiency increases protein breakdown, hyperglucagonemia is primarily responsible for the increased leucine oxidation and RMR seen during insulin deprivation.
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PMID:Role of hyperglucagonemia in catabolism associated with type 1 diabetes: effects on leucine metabolism and the resting metabolic rate. 979 44


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