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)

Adult rats were rendered diabetic by a single iv injection of streptozotocin (70 or 75 mg/kg). In these rats, serum insulin fell to minimal levels during the 48 h following drug treatment, and this was roughly paralleled by a progressive decrease in the ability of the lung to oxidize glucose. The addition of insulin to diabetic rat lung slices in vitro had no restorative effect on the depressed glucose oxidative rate during a 2 h incubation period; however, two daily treatments of the rats with 1 unit of protamine, zinc insulin completely restored lung glucose oxidation rate to normal, without significantly reducing the hyperglycemic state of the rats. An examination of the temporal changes in glucose utilization by the rat lung after acute insulin treatment revealed that the diabetic lung responded directly to serum levels of insulin, whereas the normal lung appeared to be unaffected by serum insulin levels as hihg as 87 ng/ml. The reduced rate of glucose oxidation in the diabetic lung was apparent after perfusion of the lung with glucose-free medium, and was characterized by a significant reduction in Vmax without an alteration in Km. This was attended by a depressed ability of the lung to incorporate [3H]leucine into protein and an increased ability to produce lactate, but hexose monophosphate shunt activity was normal. Specific receptors for insulin have been identified and partially characterized in crude membrane preparations of normal rat lung. The interaction of insulin with these receptors was rapid, reversible, saturable, and was dependent upon time and temperature. The binding of labeled insulin was inhibited by low concentrations of unlabeled insulin and by high concentrations of proinsulin, whereas it was unaffected by the presence of glucagon, gastrin, prolactin, ACTH, or growth hormone in microgram amounts. These observations suggest that insulin regulates the transport and utilization of glucose in the rat lung, and that this tissue contains specific receptors for insulin.
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PMID:Pulmonary insulin responsivitiy: in vivo effects of insulin on the diabetic rat lung and specific insulin binding to lung receptors in normal rats. 14 46

Investigation of glucagon secretion in isolated Wistar rat islets was carried out to elucidate further the regulatory function of glucose and arginine on pancreatic A-cells. The suppressive effect of D-glucose could also be demonstrated with L-glucose, D-mannose, D-fructose, D-galactose, D-glyceraldehyde and DL-dihydroxyacetone, but not in the presence of 3-O-methylglucose or mannitol. Sugars other than D-glucose inhibited glucagon secretion only at much higher concentrations than those at which D-glucose was effective. Furthermore, although 7.5 mM D-glucose up to 80% inhibition, the effects of other sugars appeared to level off at only 50--60% inhibition. The inhibitory action of D-glucose or D-glyceraldedyde on glucagon secretion could not be overcome by L-arginine, but 3-O-methylglucose, mannoheptulose, 2-deoxy-D-glucose, iodoacetamide, theophylline, epinephrine and acetylcholine were effective. The insulin secretion in response to glucose was inhibited by the metabolic inhibitors used, whereas the B-cell response in the presence of glyceraldehyde was diminished by iodoacetamide only. Like D-glucose, a variety of other sugars markedly reduced the stimulatory effect of L-arginine in glucagon release. The results show that the suppression of glucagon secretion is not specific for D-glucose and not strongly connected on a stimulated insulin secretion.
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PMID:Investigations on isolated islets of langerhans in vitro. 16.Modification of the glucose-dependent inhibition of glucagon secretion. 33 69

In the first part of the study oral glucose tolerance tests (GTT) or insulin tolerance tests (ITT) were performed in 22 lean and 22 obese nondiabetics before and after fasts of at least 6 days' duration. Deterioration of glucose tolerance was greater in lean than in obese individuals. Plasma levels of factors known to influence glucose tolerance (glucagon, growth hormone, free fatty acids, ketones) were significantly higher in fasting lean than in fasting obese subjects. Furthermore, delayed insulin rise (GTT) and decreased insulin sensitivity (ITT) were observed after starvation in lean subjects but not in the obese, which could explain the greater deterioration of glucose tolerance in the lean population. In the second part of the study glucose and fructose tolerance were compared during 4-hour infusions of these substrates (0.5 g/kg/h) in 8 normal subjects before and after two 4-day fasts. After starvation, glucose as well as fructose infusion resulted in plasma levels of the infused hexose significantly higher than in control, and the rise in plasma lactate and pyruvate was delayed. These results contradict the view widely held in the literature, that fructose metabolism remains unimpaired in the fasting state.
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PMID:[Carbohydrate intolerance during complete fasting]. 33 74

Parenchymal cells from adult rat liver, isolated by a collagenase perfusion technique, have been maintained in primary culture and a detailed study on carbohydrate metabolism carried out over the initial 48-hour culture period. The glucose concentration of the medium exerts a major influence on glycogen accumulation by the cells. Insulin, particularly at high glucose concentrations, stimulates glycogen biosynthesis, whereas glucagon prevents glycogen accumulation. Dexamethasone was without effect on glycogen metabolism. Glucose appears to stimulate glycogen accumulation by activation of glycogen synthetase enzyme. However, there is a gradual loss of synthetase activity throughout the culture period. Similar decreases in activity were noted for pyruvate kinase, aldolase and hexokinase. Glucose, insulin and dexamethasone were unable to prevent these decreases in enzyme activity. Foetal bovine serum contains fructose and this hexose appears to be the factor in serum which is responsible for the activation of glycogen accumulation in the presence of physiological glucose concentrations. The lactic acid content of the serum may also stimulate glycogen accumulation. In general, there is a gradual loss of the pattern of carbohydrate metabolism typical of differentiated hepatocytes during the culture period.
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PMID:Effects of hormones and serum on glycogen metabolism in adult rat liver parenchymal cell primary cultures. 40 98

The possible role of the hepatic fructose-6-phosphate substrate cycle (phosphofructokinase, fructose-1,6-diphosphatase) in the rapid hormonal regulation of gluconeogenesis was investigated in vivo in fasted normal and adrenalectomized rats after administration of [3-3H, U-14C]- or [3-3H, 6-14C]glucose. The plasma glucose 3H/14C ratio was used as an index of substrate cycling because the amount of 3H loss from liver hexose phosphates is determined by the extent of cycling. PFK and FDPase activities limit 3H loss during gluconeogenesis and glycolysis, respectively. Glucagon-stimulated hepatic glucose production is always accompanied by increased substrate cycling, i.e., increased FDPase and PFK activities. The high PFK activity may be a secondary event due possibly to elevated cellular fructose-6-phosphate levels. Decreased substrate cycling, i.e., lowered FDPase activity, always accompanies the depressed hepatic glucose production that occurs during hyperglycemia. Glucagon has no effect on substrate cycling in adrenalectomized rats that are insensitive to the hormone. The in vivo experiments presented provide evidence, although indirect, that glucagon administration results in changes in the fructose-6-phosphate substrate cycle in a living animal. Whether these changes are primary regulatory events or occur secondarily to hormone actions elsewhere is not known.
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PMID:Fructose-6-phosphate substrate cycling and hormonal regulation of gluconeogenesis in vivo. 69 24

In order to examine the role of fructose 2,6-bisphosphate (Fru-2,6-P2) in non-esterified-fatty-acid-stimulated gluconeogenesis, Fru-2,6-P2 levels were measured in cultured rat hepatocytes under conditions mimicking the fasted state. After addition of either 1.5 mM-palmitate or 10 nM-glucagon, [U-14C]lactate incorporation into glucose increased 2-fold, but only glucagon suppressed Fru-2,6-P2. Prevention of palmitate oxidation with a carnitine palmitoyltransferase-I inhibitor (2-bromopalmitate) diminished glucose production and Fru-2,6-P2 levels. Addition of exogenous glucose to the media increased Fru-2,6-P2 in a dose-related manner, which was further augmented by addition of palmitate. When Fru-2,6-P2 levels were examined in cells cultured under conditions mimicking the fed state (significantly higher basal Fru-2,6-P2 levels and lower glucose production), palmitate oxidation was associated with a significant fall in Fru-2,6-P2. In conclusion, the present studies have demonstrated a dissociation between fatty-acid-stimulated gluconeogenesis and changes in Fru-2,6-P2 in cultured rat hepatocytes. Further experiments suggest that the accumulation of intracellular hexose 6-phosphate as a result of fatty-acid-stimulated gluconeogenesis masks a putative inhibitory effect of fatty acids on Fru-2,6-P2 concentrations.
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PMID:Evidence for dissociation of gluconeogenesis stimulated by non-esterified fatty acids and changes in fructose 2,6-bisphosphate in cultured rat hepatocytes. 144 59

Amylin, a peptide found in pancreatic amyloid deposits, may be involved in NIDDM. The effects of biosynthetic human amylin on multiple aspects of carbohydrate metabolism were studied in freshly isolated and cultured liver cells (rat hepatocytes and HepG2 cells). Acute exposure of culture liver cells to amylin had no effect on glucose incorporation into glycogen. Amylin directly reduced glucose oxidation through the hexose monophosphate shunt. The glycolytic pathway was unaffected. Amylin stimulated both glycogenolysis and gluconeogenesis. These effects were largest at amylin concentrations of 1-10 pM. Insulin partially inhibited both of these responses. Glucagon stimulated glycogenolysis and gluconeogenesis to a similar extent as amylin but required concentrations 100- to 500-fold as high. Thus, amylin, at physiologic concentrations, can impair some aspects of glucose use in liver cells and is also capable of directly stimulating glucose production, suggesting a possible involvement of amylin in the impaired glucose disposal and elevated hepatic glucose output of NIDDM.
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PMID:In vitro effects of amylin on carbohydrate metabolism in liver cells. 162 73

Ligation of the pancreatic duct in rabbits provokes a decrease in the insulin and glucagon content of the pancreas, and may lead to chronic hyperglycemia. The insulin secretory behavior of the perfused pancreas is perturbed in duct-ligated animals, and this is illustrated in several respects: 1. The steady-state insulin output evoked by L-leucine (10 mM) is higher in duct-ligated than control rabbits; 2. In the presence of the amino acid, the response to D-glucose is characterized by a delayed onset, the absence of an early secretory peak, and a sluggish return towards basal value upon removal of the hexose from the perfusate; and 3. Whereas control rabbits display a higher secretory response to alpha- than beta-D-glucose, such is no more the case in duct-ligated rabbits. The perturbation of the anomeric specificity in secretory response is most obvious in diabetic duct-ligated rabbits, in which case beta-D-glucose stimulates insulin release more efficiently than alpha-D-glucose. In both control and duct-ligated rabbits, however, the alpha-anomer is more potent than the beta-anomer in suppressing leucine-stimulated glucagon secretion. These findings are compatible with the view that chronic hyperglycemia leads to alteration in the anomeric preference of the pancreatic B-cell for alpha-D-glucose, possibly as a result of the nonenzymatic glycation of glycolytic enzymes in insulin-producing, but not glucagon-producing, islet cells.
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PMID:Altered anomeric specificity of glucose-induced insulin release in rabbits with duct-ligated pancreas. 203 26

The structure-activity relationship of sugars inducing secretion of glucagon-like peptide-1 from the gut was examined using intestinal loops prepared from the terminal portion of the ileum of dogs. The plasma glucagon-like peptide-1 concentration in a mesenteric vein draining only the looped region of the intestine was increased after infusion of 139 mmol/l solutions of D-glucose, D-galactose, D-glucuronic acid, 3-0-methyl-D-glucose, maltose, sucrose or maltitol into the intestinal lumen, but not after infusion of solutions of D-fructose, D-fucose, D-mannose, D-xylose or lactose. The increases in plasma glucagon-like peptide-1 concentration correlated with the corresponding increases in glucagon-like immunoreactivity induced by these sugars. The plasma glucose level of the regional mesenteric vein increased significantly from the basal level after instillation of D-glucose, but not after instillation of other sugars. It is suggested that cells of the gut have a glucose sensor for release of products of the glucagon gene and that this sensor has specific steric requirements. The sugars that induced glucagon-like peptide-1 release share the molecular features of electron density near C(6), an equatorial hydroxyl at C(2), and an axial hydroxyl at C(1), which could account for their recognition by the glucose sensor to initiate the releases of glucagon-like peptide-1 and glucagon-like immunoreactivity.
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PMID:Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops. 223 92

The inhibition of insulin-stimulated glucose transport by lipolytic agents was studied in isolated rat adipose cells. Two different mechanisms for the inhibition of glucose transport by lipolytic hormones and agents were distinguished by use of the antilipolytic agent prostaglandin E2 (PGE2). The inhibition of glucose transport induced by lipolytic hormones such as glucagon, catecholamines or ACTH in the presence of adenosine deaminase was antagonized by PGE2. In contrast, inhibition of hexose transport by alkylxanthines was only partially (20-30%) attenuated by PGE2, although the eicosanoid had antagonized cyclic AMP accumulation and stimulation of lipolysis in response to all tested lipolytic agents. The inhibition of glucose transport by IBMX was immediate, whereas the lipolytic hormones (isoprenaline and ACTH) exhibited a latency of 2-3 min. In addition, the inhibition induced by the lypolytic hormones disappeared after cooling of the cells to 22 degrees C, at which temperature IBMX was still inhibitory. Thus, the PGE2-sensitive component of the effect of lipolytic agents on glucose transport appears to be mediated by adenylate cyclase or its subunits Ns/Ni. The PGE2-insensitive effect of alkylxanthines probably reflects a direct interaction of the agents with a regulatory site at the transporter or a related protein.
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PMID:Prostaglandin E2 differentiates between two forms of glucose transport inhibition by lipolytic agents. 244 31


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