Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compounds with a reported in vivo and in vitro effect on the diabetogenicity of alloxan were studied with regard to the uptake of calcium in mouse islet mitochondria, with the aim of obtaining information on the susceptibility and selectivity of alloxan toxicity. A strong correlation was found between the uptake of calcium in mouse islet mitochondria, which is believed to be associated with the activation of oxidative enzymes involved in energy production and secretion of insulin, and the protection afforded by the injection of D-glucose, D-mannose, L-leucine and glucagon, and by the in vitro administration of cyclic AMP, L-glutamine and L-leucine. The effect of D-glucose was abolished by D-mannoheptulose. A correlation was also seen between reduced mitochondrial uptake of calcium and the potentiation of alloxan cytotoxicity afforded by 1.25-dihydroxycholecalciferol, methylene blue and menadione. The observations suggest an association between functional activity and alloxan cytotoxicity. The selectivity of the cytotoxic action of alloxan is believed to be dependent on a reduced mitochondrial uptake of calcium and an associated reduction of the energy production at low functional activity in the B-cells (e.g. in starvation which is well-known to potentiate the alloxan effect).
 ...
PMID:Alloxan diabetogenicity: determinants of potentiation, protection and B-cell selectivity. 254 7

Glucose transport in hamster adipocytes and its modulation by insulin and isoprenaline was characterized with the aid of the non-metabolizable hexose 3-0-methylglucose. Insulin stimulated the initial uptake rates by an increase in Vmax of the transport without any detectable change in Km. The hormone concentration producing half maximal stimulation was identical to that required in rat adipocytes. However, hamster adipocytes were much less responsive to insulin (3-fold stimulation as compared to a 12-fold stimulation in rat fat cells), and maximal transport rates were 10-fold lower than that observed in rat adipocytes. Accordingly, the number of glucose transporters, as assessed by glucose-inhibitable cytochalasin-B binding, was considerably lower in plasma membranes of hamster adipocytes. Moreover, no transporters were detected in the low-density microsomes which in insulin-sensitive cell types represent the intracellular pool of recruitable glucose transporters. The relative insulin resistance of the hamster fat cells may therefore be due to a depleted pool of intracellular glucose transporters. In the presence of adenosine, the beta-adrenoceptor agonist isoprenaline produced a moderate stimulation of the basal transport rate which was antagonized by the alpha 2-agonist clonidine. If adenosine deaminase was added in order to remove endogenous adenosine, isoprenaline inhibited the insulin-stimulated transport by 50%. In contrast to the stimulatory effects of insulin and isoproterenol, the inhibitory effect of the catecholamine was reversed by cooling the cells to 22 degrees. Glucagon produced a comparable inhibition, suggesting that the inhibitory effect was mediated by adenylate cyclase or its regulatory subunits.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modulation of glucose transport in hamster adipocytes by insulin and by beta- and alpha 2-adrenoceptor agonists. 287 8

We investigated the effect of several potential carbohydrate secretagogues, amino acids, a ketoacid, and potassium chloride on insulin, glucagon, and somatostatin release from the in vitro perfused Brockmann body of channel catfish (Ictalurus punctatus). Mannose (15 mM) stimulated the release of insulin and somatostatin. Fructose (30 mM) induced only a small and transient release of somatostatin. Galactose (15 mM) was not a secretagogue. Likewise, glyceraldehyde failed to stimulate hormone release. Among the amino acids newly tested, alanine and leucine, and also alpha-ketoisocaproic acid were without effect. A high concentration of potassium (25 mEq/liter) induced a pronounced release of insulin and glucagon and a moderate release of somatostatin. In conclusion, a striking similarity exists between catfish and higher vertebrates in their pancreatic endocrine response to hexoses; on the other hand, the catfish Brockmann body appears to respond only to a few of the common stimuli of pancreatic hormone release in mammals.
 ...
PMID:Secretagogues for pancreatic hormone release in the channel catfish (Ictalurus punctatus). 288 40

We have evaluated the potential of the clonal insulin-secretory cell line HIT-T15 as a model system for investigating stimulus-secretion coupling in pancreatic B cells. In contrast to other cell lines, HIT cell insulin secretion was consistently stimulated 2- to 3-fold by D-glucose. The maximally effective concentration of glucose was 10 mmol/l; between 2 and 10 mmol/l glucose the increase in insulin release was paralleled by an increased rate of glucose oxidation. The main characteristics of glucose-stimulated insulin release by HIT cells were essentially similar to those of normal islets. Thus, the response was specific for metabolizable sugars (D-mannose and D-glyceraldehyde stimulated insulin release but L-glucose and D-galactose were ineffective); markedly dependent on extracellular Ca2+ concentration; potentiated by forskolin, glucagon, acetylcholine and 12-O-tetradecanoyl phorbol 13-acetate; inhibited by adrenaline or somatostatin; showed a biphasic pattern of release in perifusion experiments, with both phases being potentiated by forskolin. The secretory response of the HIT cells to amino acids was also similar to that of normal islets. Thus, L-leucine and its deamination product 2-ketoisocaproate were effective stimuli, whereas L-isoleucine and L-glutamine were ineffective. Insulin release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/l. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterization of the secretory system.
 ...
PMID:Insulin secretory responses of a clonal cell line of simian virus 40-transformed B cells. 302 78

The perfused pancreas of lean and obese Zucker rats was exposed, in the presence of L-leucine, to the anomers of D-glucose, which were administered on four successive occasions in the alpha/beta/alpha/beta or beta/alpha/beta/alpha sequence. In 5 lean and 6 obese rats, alpha-D-glucose was more efficient than beta-D-glucose in both stimulating insulin secretion and suppressing glucagon release. Although D-glucose evoked a greater release of insulin and, during prolonged exposure to the hexose, a less pronounced suppression of glucagon secretion in obese than lean rats, the anomeric specificity of these secretory responses was not different in the two groups of animals. In one lean rat, however, alpha-D-glucose, while efficiently stimulating insulin release, failed on two occasions to inhibit glucagon secretion. This isolated observation raises the possibility that the anomeric specificity of functional events evoked by D-glucose in the endocrine pancreas may occasionally be perturbed.
 ...
PMID:Anomeric specificity of the insulin and glucagon secretory responses to D-glucose in lean and obese Zucker rats. 332 84

The role of glucose metabolism in sperm cell motility was examined in purified human spermatozoa from the perspective of elucidating its possible significance in spontaneous and experimental diabetes. After a 4-h incubation in the absence of D-glucose, the mean progressive velocity of human spermatozoa was 40% lower than that of control cells kept in the presence of D-glucose. The decline was rapidly overcome by the addition of D-glucose or D-fructose, the amplitude of this stimulatory effect being independent of the ambient hexose concentration. Between 1.4 and 16.7 mM glucose, spermatozoal glucose oxidation also proceeded independently of the extracellular glucose levels, whereas both insulin (100nM) and glucagon (100nM) failed to significantly affect the rate of glucose metabolism or cellular motility. It is speculated from these results that an alteration in seminal hexose concentrations or pancreatic hormone levels may be an unlikely cause for the reduced sperm motility that is characteristically observed in diabetic patients. Human spermatozoa rapidly incorporated D-glucose and 3-O-methyl-D-glucose but excluded the glucose-analogue alloxan, which may explain their resistance against the toxic effects of this diabetogenic drug, in spite of their intrinsic sensitivity to organic peroxides such as tert-butyl hydroperoxide.
 ...
PMID:Glucose metabolism in human spermatozoa: lack of insulin effects and dissociation from alloxan handling. 351 12

The antiprotozoal drug pentamidine can be toxic to islet cells in vivo and in vitro. Rat islets were exposed to pentamidine (mesylate and isethionate salts) and six other structurally related diamidines. The beta-cell response to arginine + theophylline was suppressed by pentamidine (10(-2) mmol/l) while the glucagon and somatostatin secretions persisted. All diamidines tested suppressed the beta-cell function, with a log-dose-response proportionality, the mesylate compound being more potent than pentamidine isethionate, and the lipophilic analogs more than the hydrosoluble diamidines. Electron microscopy revealed distinct morphological alterations in islets exposed to pentamidine, the intensity of these changes being dose-and time-dependent, and the beta cells more severely damaged than the non-beta cells. 51Cr-labelled islet cells and RIN 5 F cells consistently appeared more sensitive to pentamidine cytotoxicity than rat fibroblasts, myeloma cells and hepatocytes. The pentamidine-induced suppression of beta-cell function was not, in conditions tested, affected by the presence of nicotinamide and the hexose concentration in the medium. The kinetics of islet damage were slower than those of streptozotocin and alloxan-induced islet damage. The present study confirms that pentamidine is selectively toxic to islet beta cells, with some features distinct from the alloxan and streptozotocin toxicities to these cells. The mechanism of this process and its precipitating factors in vivo need clarification.
 ...
PMID:Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro. 389 20

1. Rates of glucose oxidation, lactate output and the intracellular concentration of glucose 6-phosphate were measured in mouse pancreatic islets incubated in vitro. 2. Glucose oxidation rate, measured as the formation of (14)CO(2) from [U-(14)C]glucose, was markedly dependent on extracellular glucose concentration. It was especially sensitive to glucose concentrations between 1 and 2mg/ml. Glucose oxidation was inhibited by mannoheptulose and glucosamine but not by phlorrhizin, 2-deoxyglucose or N-acetylglucosamine. Glucose oxidation was slightly stimulated by tolbutamide but was not significantly affected by adrenaline, diazoxide or absence of Ca(2+) (all of which may inhibit glucose-stimulated insulin release), by arginine or glucagon (which may stimulate insulin release) or by cycloheximide (which may inhibit insulin synthesis). 3. Rates of lactate formation were dependent on the extracellular glucose concentration and were decreased by glucosamine though not by mannoheptulose; tolbutamide increased the rate of lactate output. 4. Islet glucose 6-phosphate concentration was also markedly dependent on extracellular glucose concentration and was diminished by mannoheptulose or glucosamine; tolbutamide and glucagon were without significant effect. Mannose increased islet fructose 6-phosphate concentration but had little effect on islet glucose 6-phosphate concentration. Fructose increased islet glucose 6-phosphate concentration but to a much smaller extent than did glucose. 5. [1-(14)C]Mannose and [U-(14)C]fructose were also oxidized by islets but less rapidly than glucose. Conversion of [1-(14)C]mannose into [1-(14)C]glucose 6-phosphate or [1-(14)C]glucose could not be detected. It is concluded that metabolism of mannose is associated with poor equilibration between fructose 6-phosphate and glucose 6-phosphate. 6. These results are consistent with the idea that glucose utilization in mouse islets may be limited by the rate of glucose phosphorylation, that mannoheptulose and glucosamine may inhibit glucose phosphorylation and that effects of glucose on insulin release may be mediated through metabolism of the sugar.
 ...
PMID:Glucose metabolism in mouse pancreatic islets. 491 69

Arterial (A) and renal venous (RV) concentrations and net splanchnic exchange of glucose, fructose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during a 135-min intravenous infusion of fructose at 2 mmol/min in healthy subjects after a 60-h fast. After 45 min of the fructose infusion, somatostatin (9 microgram/min) was infused for 60 min to induce hypoglucagonemia. Fructose infusion resulted in a net uptake of this hexose by the kidney as well as the splanchnic bed. Estimated renal uptake of fructose could account for the disposal of 20% of the administered fructose load while splanchnic uptake accounted for 38%. The fructose infusion resulted in a rise in blood glucose of 0.9 mmol/L, a 35% increase in net glucose output from the splanchnic bed, and a consistent net output of glucose from the kidney (A-RV = -0.17 +/- 0.05 mmol/L as compared with 0 +/- 0.03 in the basal state, P less than 0.02). Net glucose release from the kidney could account for 55% of the net renal uptake of fructose. The fructose infusion also resulted in a marked change in renal lactate balance from a net uptake in the basal state (A - RV = 0.05 +/- 0.01 mmol/L) to a net output during fructose administration (A - RV = -0.10 +/- 0.04). Administration of somatostatin resulted in a fall in arterial glucagon levels and a 35% decrease in splanchnic glucose output but failed to alter the arterial-renal venous difference for glucose observed during the fructose infusion. We conclude that in 60-h fasted man: (a) intravenous infusion of fructose results in a net uptake of this hexose by the kidney as well as the liver, (b) this uptake is accompanied by stimulation of renal as well as hepatic glucose production and renal production of lactate, and (c) hypoglucagonemia inhibits splanchnic but not renal glucose output during fructose infusion. These data indicate that the kidney is an important site of fructose disposal and that glucose and lactate are end products of renal fructose metabolism.
 ...
PMID:Role of the kidney in the metabolism of fructose in 60-hour fasted humans. 613 22

Glucose exerts opposite effects upon glucagon and insulin release from the endocrine pancreas. Glucose uptake and oxidation were therefore compared in purified A- and B-cells. In purified B-cells, the intracellular concentration of glucose or 3-O-methyl-D-glucose equilibrates within 2 min with the extracellular levels, and, like in intact islets, the rate of glucose oxidation displays a sigmoidal dose-response curve for glucose. In contrast, even after 5 min of incubation, the apparent distribution space of D-glucose or 3-O-methyl-D-glucose in A-cells remains much lower than the intracellular volume. In A-cells, both the rate of 3-O-methyl-D-glucose uptake and glucose oxidation proceed proportional to the hexose concentration up to 10 mM and reach saturation at higher concentrations. Addition of insulin failed to affect 3-O-methyl-D-glucose or D-glucose uptake and glucose oxidation by purified A-cells. Glucose releases 30-fold more insulin from islets than from single B-cells, but this marked difference is not associated with differences in glucose handling. The rate of glucose oxidation is virtually identical in single and reaggregated B-cells and is not altered after addition of glucagon or somatostatin. It is concluded that the dependency of glucose-induced insulin release upon the functional coordination between islet cells is not mediated through changes in glucose metabolism.
 ...
PMID:Differences in glucose handling by pancreatic A- and B-cells. 614 Nov 62


<< Previous 1 2 3 4 5 Next >>