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)

We hypothesized that augmented responses of glucoregulatory hormones in iron deficiency would enhance liver and muscle glycogenolysis, leading to increased gluconeogenic precursor (lactate) supply and upregulation of hepatic gluconeogenesis. Female weanling rats were randomly placed on either a mildly iron-deficient (-Fe; 15 mg Fe/kg diet) or an iron-sufficient (+Fe; 50 mg Fe/kg diet) diet for 4 wk and studied at rest and during exhaustive treadmill running. Hemoglobin was 9.0 +/- 0.2 and 13.1 +/- 0.3 g/dl in -Fe and +Fe, respectively, after 3.5 wk of dietary iron deficiency. Arterial plasma epinephrine (Epi), norepinephrine (NE), adrenocorticotropic hormone (ACTH), corticosterone, insulin, and glucagon levels were similar at rest in both groups, as were liver, gastrocnemius, and superficial and deep vastus medialis glycogen levels. Liver and kidney phosphoenolpyruvate carboxykinase (PEPCK) activities were similar in both groups. Maximum O2 consumption was decreased (22%) in -Fe. Respiratory exchange ratio (CO2 production/O2 consumption) was unaffected at rest but increased at maximum O2 consumption in -Fe. Time to exhaustion during a standardized running test (13.4 m/min, 0% grade) was decreased 45% in -Fe (63 +/- 5 vs. 116 +/- 10 min). During exercise, euglycemia was maintained in both groups, but blood lactate was elevated in -Fe. The mean net glycogen utilization during exercise was increased in liver (43%), soleus (33%), and superficial vastus medialis (106%) and decreased in the gastrocnemius (36%) in -Fe. Liver and kidney PEPCK activities were increased similarly at exhaustion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Augmented glucoregulatory hormone concentrations during exhausting exercise in mildly iron-deficient rats. 823 58

Oxygen modulates the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene. The respiratory chain or heme proteins have been proposed to function as O2-sensors. The functions of the respiratory chain are impaired by uncouplers such as 2,4-dinitrophenol (DNP); those of ferro-heme proteins are affected by carbon monoxide (CO), which locks heme in the oxy conformation. Therefore, the effects of different concentrations of CO and DNP on the glucagon-dependent induction of PCK mRNA and PCK activity were investigated at different physiological oxygen tensions in primary rat hepatocyte cultures. The cells were cultured under standard conditions from 4-24 h. After addition of fresh media PCK was induced with 1 nM glucagon. PCK mRNA and PCK activity were elevated after 2h and 3h, respectively, to 100% at 16% O2 (mimicking arterial oxygen tensions) and to about 60% at 8% O2 (mimicking venous oxygen tensions). CO counteracted the reduced induction at lower oxygen tensions: Under 8% O2 + 2% CO PCK mRNA could be elevated again to about 90% and PCK activity to about 80%. CO did not impair the induction by insulin of ornithine decarboxylase (ODC) and the incorporation of 14C-leucine into total protein. CO did not cause lactate dehydrogenase (LDH) to leak from the cells or influence the cell structures at the microscopical level. DNP (50 microM) unspecifically lowered PCK gene expression without affecting its modulation by oxygen. These results are in line with the proposal that a ferro-heme protein rather than the respiratory chain acted as an O2 sensor in the activation of the PCK gene.
 ...
PMID:A ferro-heme protein senses oxygen levels, which modulate the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. 837 14

Glucose production and oxidation were measured in ventilated preterm appropriate-for-gestational-age and small-for-gestational-age infants on the first day of life. Using a new technique of NaH13CO3 infusion followed by a [U-13C]glucose infusion, we measured glucose oxidation rates without measuring the CO2 production rate. Infants were studied at 18 +/- 4 h (mean +/- 1 SD) of life and received parenterally administered glucose only (4.2 +/- 0.5 mg.kg-1 x min-1). In 13 of 16 patients, the glucose production rate exceeded 1.0 mg.kg-1 x min-1. Infants born from mothers who had been receiving steroids antenatally had higher glucose production rates (2.3 +/- 1.1 mg.kg-1 x min-1) compared with infants from mothers who had not (1.1 +/- 0.8 mg.kg-1 x min-1, p = 0.036). The glucose oxidized (2.9 +/- 1.0 mg.kg-1 x min-1) was lower than the amount of glucose infused (p = 0.005) and was not different for appropriate-for-gestational-age and small-for-gestational-age infants. Plasma levels of glucose, insulin, glucagon, and total IGF-I were not correlated with glucose metabolism on the first day of life. Total IGF-II levels were negatively correlated with the rate of glucose appearance. We conclude that preterm infants on the first day of life receiving a glucose infusion of 4.2 mg.kg-1 x min-1 continue to produce glucose. The glucose oxidation rate is lower than the glucose infusion rate and the contribution of glucose oxidation to the total energy expenditure is limited.
 ...
PMID:Glucose kinetics and glucoregulatory hormone levels in ventilated preterm infants on the first day of life. 837 16

Antidiuretic hormone and parathyroid hormone (PTH) inhibit HCO3- absorption by the rat medullary thick ascending limb (MTAL). Studies were performed on rat MTAL tubule suspension to specify the H(+)-HCO3- membrane transporters affected by these hormones and the implicated intracellular second messengers. Arginine vasopressin (AVP) and PTH stimulated cell adenosine 3',5'-cyclic monophosphate (cAMP) production with a relative rank order potency of AVP > rat PTH-(1-34) > bovine PTH-(1-84). Significant cell acidification in HCO3- -CO2-free medium, monitored in 2'7'-bis(carboxyethyl)-5(6')-carboxyfluorescein-loaded cells, was caused by 0.1 nM AVP, 1 nM rat PTH-(1-34), but not by < 100 nM bovine PTH-(1-84), as well as by 10(-4) M 8-bromo-cAMP and 2 x 10(-5) M forskolin; 10 nM AVP or rat PTH-(1-34) did not alter the intracellular pH when Na+/H+ antiport was inhibited by 2 mM amiloride. Prostaglandin E2 (PGE2, 10(-6) M), which inhibited AVP-stimulated cell cAMP production, reduced by 35% the cell acidification response to 10 nM AVP. AVP and 8-bromo-cAMP inhibited Na+/H+ antiport-dependent cell pH recovery from intracellular acidification, which was explained by a decrease in the Vmax of the antiporter. AVP did not directly affect K(+)-HCO3- cotransport and plasma membrane H(+)-ATPase of rat MTAL cells. Cytosolic calcium ([Ca2+]i), monitored in fura-2-loaded cells, was unaffected by up to 1 nM AVP, 100 nM PTH, glucagon, calcitonin, and oxytocin, and 1 microM PGE2; however, 100 nM AVP, but not 1-desamino-8-D-AVP (dDAVP), caused a peak increase in [Ca2+]i, even in the absence of extracellular Ca2+, and stimulated cell accumulation of [3H]inositol phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:cAMP-dependent control of Na+/H+ antiport by AVP, PTH, and PGE2 in rat medullary thick ascending limb cells. 838 52

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-13C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO2 production during GLP-1 administration (P < 0.0005). Plasma insulin increased after 3h of GLP-1 infusion to 1486 +/- 145 pmol L(-1) vs. 185 +/- 12 pmol L(-1) for saline (P < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.
 ...
PMID:Effects of glucagon-like peptide 1 (7-36 amide) on whole-body protein metabolism in healthy man. 904 71

Previous studies in rat islets have suggested that anaplerosis plays an important role in the regulation of pancreatic beta cell function and growth. However, the relative contribution of islet beta cells versus non-beta cells to glucose-regulated anaplerosis is not known. Furthermore, the fate of glucose carbon entering the Krebs cycle of islet cells remains to be determined. The present study has examined the anaplerosis of glucose carbon in purified rat beta cells using specific 14C-labeled glucose tracers. Between 5 and 20 mM glucose, the oxidative production of CO2 from [3,4-14C]glucose represented close to 100% of the total glucose utilization by the cells. Anaplerosis, quantified as the difference between 14CO2 production from [3,4-14C]glucose and [6-14C]glucose, was strongly influenced by glucose, particularly between 5 and 10 mM. The dose dependence of glucose-induced insulin secretion correlated with the accumulation of citrate and malate in beta(INS-1) cells. All glucose carbon that was not oxidized to CO2 was recovered from the cells after extraction in trichloroacetic acid. This indirectly indicates that lactate output is minimal in beta cells. From the effect of cycloheximide upon the incorporation of 14C-glucose into the acid-precipitable fraction, it could be calculated that 25% of glucose carbon entering the Krebs cycle via anaplerosis is channeled into protein synthesis. In contrast, non-beta cells (approximately 80% glucagon-producing alpha cells) exhibited rates of glucose oxidation that were (1)/(3) to (1)/(6) those of the total glucose utilization and no detectable anaplerosis from glucose carbon. This difference between the two cell types was associated with a 7-fold higher expression of the anaplerotic enzyme pyruvate carboxylase in beta cells, as well as a 4-fold lower ratio of lactate dehydrogenase to FAD-linked glycerol phosphate dehydrogenase in beta cells versus alpha cells. Finally, glucose caused a dose-dependent suppression of the activity of the pentose phosphate pathway in beta cells. In conclusion, rat beta cells metabolize glucose essentially via aerobic glycolysis, whereas glycolysis in alpha cells is largely anaerobic. The results support the view that anaplerosis is an essential pathway implicated in beta cell activation by glucose.
 ...
PMID:Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. 922 23

Recent observations suggest that carbon monoxide (CO) may serve as a neuroendocrine modulator in hypothalamus. Here we provide evidence, for the first time, that the islets of Langerhans contain the constitutive isoform of the CO-producing enzyme heme oxygenase (HO-2), the activity of which was found to modulate islet hormone release. Most insulin and glucagon cells in the rat endocrine pancreas expressed strong immunoreactivity for HO-2. In the exocrine parenchyma, scattered HO-2-positive ganglionic cell bodies were occasionally observed. Furthermore, Western blot analysis revealed the presence of HO-2 in isolated islets but not in acinar cells. Islet homogenates displayed a comparatively high HO-2 enzymatic activity measured as CO formation (approximately 600 pmol CO.min-1.mg islet protein-1). This HO-2 enzymatic activity was greatly suppressed by zincprotoporphyrin-IX (ZnPP-IX), a recognized inhibitor of HO activity. Neither ZnPP-IX nor the HO activator, hemin, influenced basal insulin release from isolated rat islets at low (1 mM) glucose. However, glucagon release at 1 mM glucose was increased by hemin and inhibited by ZnPP-IX. The hemin-induced increase in glucagon secretion was abolished by ZnPP-IX. Furthermore, a series of experiments at high glucose (16.7 mM) revealed that hemin induced a dose-dependent potentiation of glucose-stimulated insulin release. Moreover, glucose-induced insulin release was dose-dependently suppressed by ZnPP-IX but unaffected by protoporphyrin-IX, a compound known not to influence HO-2 activity in other tissues. Similarly, glucagon release at high glucose was dose-dependently increased by hemin and suppressed by ZnPP-IX. Finally, the hemin-induced increase in islet hormone release at high glucose was totally abolished by ZnPP-IX. The data strongly suggest that CO production positively modulates both glucagon and insulin secretion. We propose that CO may serve as a novel messenger molecule within the islets of Langerhans.
 ...
PMID:Occurrence and putative hormone regulatory function of a constitutive heme oxygenase in rat pancreatic islets. 927 68

The incretin hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is best known for its antidiabetogenic actions mediated via a GLP-1 receptor present on pancreatic endocrine cells. To investigate the molecular mechanisms of GLP-1 action in muscle, we used cultured L6 myotubes. In L6 myotubes, GLP-1 enhanced insulin-stimulated glycogen synthesis by 140% while stimulating CO2 production and lactate formation by 150%. In the presence of IBMX, GLP-1 diminished cAMP levels to 83% of IBMX alone. In L6 myotubes transfected with pancreatic GLP-1 receptor, GLP-1 increased cAMP levels and inhibited glycogen synthesis by 60%. An antagonist of pancreatic GLP-1 receptor, exendin-4-(9-39), inhibited GLP-1-mediated glycogen synthesis in GLP-1 receptor-transfected L6 myotubes. However, in parental L6 myotubes, exendin-4-(9-39) and GLP-1-(1-36) amide, an inactive peptide on pancreatic GLP-1 receptor, displaced 125I-labeled GLP-1 binding and stimulated glycogen synthesis by 186 and 130%, respectively. These results suggest that the insulinomimetic effects of GLP-1 in L6 cells are likely to be mediated by a receptor that is different from the GLP-1 receptor found in the pancreas.
 ...
PMID:GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor. 973 Sep 51

The uptake and metabolism of glucose were assessed in enterocytes isolated from black bullhead Ictalurus melas. The objective of this study was to examine the effects of diet and hormone treatment on glucose transport and metabolism, so the enterocyte was the most appropriate preparation. Glucose transport was estimated using specific inhibitors: glucose uptake measured in the presence of phlorizin presumably represents transport at the basolateral membrane, whereas glucose uptake in the presence of cytochalasin B presumably represents transport at the brush border. Feeding bullheads a standard diet resulted in maximum enterocyte rates of glucose uptake of 438.2+/-35.5 nmol mg-1 cells h-1 for transport in the presence of cytochalasin B and 427.0+/-49.7 nmol mg-1 cells h-1 (means +/- s.e.m., N=12) for transport in the presence of phlorizin. These values represent 50 % of the total 3-O-methylglucose transported. The rate of transport in the presence of cytochalasin B was increased in bullheads fed a high-carbohydrate diet. Incubating bullhead enterocytes with glucagon or glucagon-like peptide-1 (GLP) at 10(-8 )mol l-1 and with dexamethasone or isoproterenol at 10(-6 )mol l-1 significantly increased the rate of brush-border transport, but not the apparent affinity constant (Kt). Activation was dependent on hormone concentration. In contrast, insulin was without effect on transport rates, nor did it counteract activation by glucagon-family peptides. CO2 production rates from d-[14C]glucose indicated that glucose metabolism was not limited by transport rates in the enterocytes. Glucagon and GLP decreased maximal oxidation rates, whereas dexamethasone, isoproterenol and insulin did not alter these rates. The activities of enterocyte hexokinase exceeded the rate of glucose oxidation but not the rate of transport of glucose, at least at maximum activities, implicating this enzyme as one component of the strategy to ensure that glucose is maximally available to the blood of this species.
 ...
PMID:Transport and metabolism of glucose in isolated enterocytes of the black bullhead ictalurus melas: effects of diet and hormones 980 39

Carbon monoxide (CO) has been suggested as a novel messenger molecule in the brain. We now report on the cellular localization and hormone secretory function of a CO-producing constitutive heme oxygenase (HO-2) in mouse islets. Islet homogenates produced large amounts of CO which were suppressed dose-dependently by the HO inhibitor zincprotoporphyrin-IX (ZnPP-IX). We also show, for the first time, that glucose markedly stimulates the HO activity (CO production) in intact islets. A further potentiation was induced by the HO substrate hemin. Western blot showed that islet tissue expressed HO-2, and confocal microscopy revealed that HO-2 resided in insulin, glucagon, somatostatin, and pancreatic polypeptide cells. ZnPP-IX dose-dependently inhibited, whereas hemin enhanced, both insulin and glucagon secretion from glucose-stimulated islets. Stimulation or inhibition of CO production was accompanied by corresponding changes in islet cGMP levels. Exogenously applied CO stimulated insulin and glucagon release from isolated islets, whereas exogenous nitric oxide (NO) inhibited insulin and stimulated glucagon release. Islets stimulated by glucose or L-arginine displayed a marked increase in their NO-synthase (NOS) activity. Such an increase was suppressed by hemin, conceivably because NOS activity was inhibited by hemin-derived CO. Consequently, hemin enhanced L-arginine-induced insulin secretion. Insulin release stimulated by either hemin-derived CO or exogenous CO was strongly inhibited by the guanylate cyclase inhibitor ODQ, but it was unaffected by ZnPP-IX. Glucagon release induced by CO (but not by hemin) was inhibited by ODQ and partly inhibited by ZnPP-IX. We propose that the islets of Langerhans are equipped with a heme oxygenase-carbon monoxide pathway, which constitutes a novel regulatory system of physiological importance for the stimulation of insulin and glucagon release. This pathway is stimulated by glucose, is at least partly dependent on the cGMP system, and displays interaction with islet NOS activity.
 ...
PMID:Heme oxygenase and carbon monoxide: regulatory roles in islet hormone release: a biochemical, immunohistochemical, and confocal microscopic study. 989 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>