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)

The metabolic effects of beta-(+/-)-2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid (BCH), a nonmetabolizable analog of leucine and known activator of glutamate dehydrogenase, were studied in hepatocytes isolated from fed and fasted rats. With glutamine as substrate, BCH stimulated in a concentration-dependent manner urea synthesis in both physiological states and glucose formation in hepatocytes from fasted rats. Despite the much higher rates of ureagenesis in the fasted animals, the degree of stimulation by BCH, over 2-fold, was similar. The effect of the drug was specific for glutamine since the rates of urea synthesis from NH4Cl, alanine, and asparagine were essentially unaltered. The stimulation of glutamine catabolism by BCH led to a decrease in the content of intracellular glutamine. The redox states of the mitochondrial and cytosolic nicotinamide adenine dinucleotides remained unaltered. In hepatocytes isolated from fasted rats and incubated with 5 mM glutamine the BCH-induced increases in urea, ammonia, and the amino acids, glutamate, aspartate, and alanine, accounted fully for the 2.4-fold rise in glutamine utilization. The stimulatory effects of BCH and glucagon on the formation of glucose, urea, and 14CO2 from [U-14C]glutamine were additive. Aminooxyacetate, and inhibitor of transaminases, neither blocked glutamine catabolism (as measured by the sum of urea, ammonia, and glutamate) nor prevented its activation by BCH. It is suggested that, in isolated hepatocytes, BCH-induced stimulation of glucose and urea formation from glutamine results from activation of glutaminase by a mechanism which is distinct from that of glucagon.
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PMID:Glutamine metabolism in rat hepatocytes. Stimulation by a nonmetabolizable analog of leucine. 377 24

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.
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PMID:Functional and morphological modifications induced in rat islets by pentamidine and other diamidines in vitro. 389 20

Intestinal ischemia shock was induced by 35 to 40-min portal vein occlusion (PVO). After treatment with rat plasma a severe hypoglycemia ensues which is caused by a block in gluconeogenesis. This hypoglycemia is not affected by treatment with adrenaline, glucagon, nicotinadenine dinucleotide (NAD), adenosine triphosphate (ATP) alanine (A), or pyruvate (P), while fructose (F) and dihydroxyacetone (DHA) slightly increase the plasma glucose concentration. If F or DHA are combined with NAD a considerable hyperglycemic effect is observed, but NAD plus A or P is ineffective. A similar marked rise in plasma glucose is observed if F is combined with nicotinamide, adenylic acid, or histamine. NAD causes vasodilatation in the splanchnic area and an increased portal flow. It is concluded that the effect of NAD is the result of an increased uptake of suitable substrates of gluconeogenesis from the peritoneal cavity and/or an increased availability of these substrates to the liver. During the development of PVO shock, portal venous flow diminishes considerably. This reduced flow may be the result of vasoconstriction caused by the high level of plasma adrenaline.
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PMID:Studies on the site of the block in gluconeogenesis causing severe hypoglycemia in intestinal ischemia shock in rats. 405 96

Catecholamines induced an increase in the activity of rat adipose tissue and liver phosphopyruvate carboxylases that was maintained for 48h. The response of adipose tissue phosphopyruvate carboxylase was blocked by actinomycin D, corticosteroids and propranolol, whereas corticosteroids and propranolol did not affect the liver enzyme. Cortisol phosphate, like actinomycin D, interfered only with the initiation of the increase in enzyme activity caused by noradrenaline, but not with the process of enzyme accumulation. In contrast, cycloheximide was effective in blocking enzyme induction throughout the course of the catecholamine effect. Adrenocorticotrophic hormone caused a short-term induction of adipose tissue phosphopyruvate carboxylase, which could be blocked by propranolol. Hepatic phosphopyruvate carboxylase, but not the adipose tissue enzyme, was induced by dibutyryladenosine 3':5'-cyclic monophosphate and by glucagon. Both nicotinic acid and nicotinamide decreased the normal induction of adipose tissue phosphopyruvate carboxylase caused by starvation, but only nicotinamide increased the activity of the liver enzyme.
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PMID:The interaction of catecholamines and adrenal corticosteroids in the induction of phosphopyruvate carboxylase in rat liver and adipose tissue. 434 97

1. The activities of NMN adenylyltransferase and of NAD(+) kinase have been measured in the livers of adrenalectomized or alloxan-diabetic rats and in the livers of rats treated with glucagon, pituitary growth hormone or thyroxine. 2. The activities of these enzymes have been compared with the effects of the same treatments on the nicotinamide nucleotide concentrations in the liver. 3. Alloxandiabetes (+37%) and thyroxine (+27%) both increased the activity of NMN adenylyltransferase. The other treatments were without effect on this enzyme. 4. Only thyroxine increased the activity of NAD(+) kinase significantly (+26%) although both adrenalectomy and glucagon tended to increase its activity. 5. The activity of NAD(+) glycohydrolase was measured in the livers of diabetic rats, and in the livers of rats treated with either growth hormone or thyroxine. Of these treatments, only growth hormone altered the enzyme activity (+26%, calculated on a total hepatic activity basis). 6. Female rats had a greater hepatic NAD(+)-kinase activity than males but there was no sex difference with respect to NMN adenylyltransferase. 7. The lack of correlation between the maximum potential activity of these three enzymes and the known changes of the nicotinamide nucleotides in each of the hormone conditions is discussed.
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PMID:The activities of nicotinamide mononucleotide adenylyltransferase and of nicotinamide-adenine dinucleotide kinase in the livers of rats subjected to different hormonal treatments. 437 8

Adrenergic mechanism for phosphorylase activation was gradually converted from an alpha 1- to a beta 2-type during primary culture of rat hepatocytes. beta 2-Receptor-mediated cAMP generation was also much greater in 8-h cultured cells than in fresh cells. Incubation of hepatocyte membranes with [alpha-32P]NAD and the preactivated A-protomer (an active component) of islet-activating protein (IAP), pertussis toxin, resulted in the ADP-ribosylation of a specific IAP substrate protein (Mr = 41,000). This ADP-ribosylation diminished progressively when the membrane-donor hepatocytes had been cultured. The early diminution was interfered with by the addition of nicotinamide or isonicotinamide, a potent inhibitor of ADP-ribosyltransferase, to the culture medium. The decrease of the IAP substrate was well correlated with the potentiation of beta-adrenergic functions under various conditions of culture. beta-Receptor-mediated activation of GTP-dependent membrane adenylate cyclase was, but glucagon-induced activation was not enhanced by either prior culture of hepatocytes or prior exposure of membranes to the A-protomer of IAP. There was no further enhancement, however, when membranes from cultured cells were exposed to the active toxin. Thus, the IAP-susceptible inhibitory guanine nucleotide-regulatory protein is coupled to beta-adrenergic receptors in such a manner as to reduce the degree of activation of cyclase, and the decrease in this IAP substrate may be responsible, at least partly, for development of beta-receptor functions during culture of hepatocytes. Its possible relation to accompanying inhibition of alpha 1-receptor functions is discussed.
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PMID:Conversion of adrenergic mechanism from an alpha- to a beta-type during primary culture of rat hepatocytes. Accompanying decreases in the function of the inhibitory guanine nucleotide regulatory component of adenylate cyclase identified as the substrate of islet-activating protein. 609 73

Rat islet cell tumours induced by injection of streptozotocin and nicotinamide have been studied in vivo and after the establishment of monolayer cultures of tumour cells. During an intravenous glucose tolerance test, tumour-bearing rats had increased release of immunoreactive insulin, with a high proportion of proinsulin, as well as accelerated glucose disposal relative to control rats. The tumours were rich in immunoreactive insulin and somatostatin, poor in glucagon. Non-tumour pancreatic tissue or isolated islets contained 10% or less of the corresponding normal amounts of insulin whereas the islet content of somatostatin was unchanged and that of glucagon increased. This is best interpreted as a selective suppression of non-tumour B cells, further supported by the observation that the initially reduced insulin release and content of non-tumour islets were partially restored after 2 days in tissue culture. In monolayer culture, tumour cells maintained insulin production and acute responsiveness to glucose for prolonged periods. There was no sign of cell proliferation. It is concluded that primary, chemically-induced insulin-producing pancreatic islet cell tumours retain several features characteristic to normal B cells and continue to influence glucose homeostasis in vivo.
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PMID:Studies in vivo and in vitro on chemically-induced primary islet cell tumours and non-tumour endocrine pancreatic tissue. 613 Oct 5

In order to identify the early stage of the development of experimental pancreatic endocrine tumors, Wistar rats were treated with streptozotocin and nicotinamide. One to 11 months after the treatment, the pancreata were examined for neoplastic lesions, using immunocytochemistry and electronmicroscopy. The earliest changes consisted of focal adenomatous proliferation of small ducts, occasionally including endocrine cell clusters. They occurred in the same frequency throughout the whole period examined, regardless whether the pancreata contained tumors or not, and were also present, though in lower numbers, in controls. Immunocytochemistry revealed no true budding off of endocrine cells from ductular epithelium. Thus the histogenetic relationship of the ductal proliferations to the endocrine tumors remains unclear. The earliest tumors were recognized at the fourth month. At the eleventh month 31% of the animals beared tumors. Insulin-positive cells predominated in the tumors, followed by somatostatin-, glucagon- and PP-positive cells. The multihormonal appearance of the neoplasmas is well comparable with the findings in human insulinomas.
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PMID:On the histogenesis of experimental pancreatic endocrine tumors. An immunocytochemical and electron microscopical study. 623 52

A serially transplantable, chemically induced pancreatic islet cell tumor was developed in Lewis rats. The original tumor was induced by the administration of streptozotocin and nicotinamide. It was subsequently maintained by ip or sc transplantation of tissue fragments into recipient animals. Tumors generally grew to 0.5--2.0 cm in diameter within 3--4 months of transplantation. They were well encapsulated, without gross evidence of metastasis. Peroxidase immunocytochemical staining revealed a predominance of insulin-positive cells. Somatostatin-positive cells were also present and varied widely in numbers between different tumors. In addition, small numbers of glucagon-positive cells were observed in all of the tumors. On electron microscopy, cells containing secretory granules, indistinguishable from nonneoplastic beta-cells, were most abundant. Other granulated cells were also observed, but the granule morphology was not identical to that of any of the other classically described islet cell types. Tumor extracts contained an average of 3260 micrograms insulin, 22.6 micrograms somatostatin, and 0.84 micrograms glucagon per g wet wt of tissue. Tumors caused marked, progressive hypoglycemia in recipients, with plasma glucose levels frequently falling below 30 mg/dl before death. Furthermore, the recipients' islets were markedly reduced in size due to a decreased beta-cell volume.
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PMID:Serially transplantable chemically induced rat islet cell tumor. 625 Aug

This paper describes an inhibitory effect of propranolol on insulin secretion in rats with pancreatic islet cell tumors which have been induced by streptozotocin (65 mg/kg body weight) and nicotinamide (500 mg/kg). Following glucose ingestion (3 g/kg), propranolol (4 mg/kg) was injected into the tumor-bearing rats. Plasma insulin decreased paradoxically despite an increase in blood glucoses. In contrast, propranolol did not suppress insulin secretion in normal rats. The drug was found to have no effect on glucagon secretion in either experimental or control animals during glucose load. This may suggest that the experimentally induced insulinoma in hypersensitive to propranolol for inhibiting insulin secretion.
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PMID:Effect of propranolol on glucose-induced insulin response in rats with insulinomas. 626 20


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