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)

We have devised a tissue culture system that permits de novo formation of islets. Neonatal rat pancreata are enzymatically dissociated into single cells. The cell suspension is filtered through polyester cloth with 20 microns pores to exclude cell aggregates as well as preformed islets and a single cell suspension is then plated into tissue culture dishes at a density precluding reaggregation. Pancreatic cells proliferate forming numerous colonies of epithelioid cells. After a confluent monolayer, cells proliferate into a third dimension, the space occupied by the culture medium. Third dimensional proliferation occurs from basal monolayers of epithelioid colonies. At about 9 days in culture, numerous hillocks are visible that are spaced at about 1 mm from one another. Islets are observed to bud from the hillock surfaces. In 1 micron-thick sections, secretion granules are detected with the light microscope in some islet cells. With the electron microscope three basic cell types are seen. One peripherally located cell type is sparsely granulated and appears to be a precursor cell. The other peripherally located cell type shows a homogeneous population of secretion granules characteristic of A-cells. The third cell type is found in the interior of islets containing granules characteristic of B-cells. Islet cells, but not hillock cells, react immunocytochemically for insulin and glucagon. The cultures secrete 2 to 10-fold the amounts of glucagon present in fresh medium. It is concluded that differentiation of A- and B-cells occurs in neoformed islets.
Mol Cell Endocrinol 1986 Nov
PMID:Islet neoformation in tissue culture. 353 38

A dramatic increase in the plasma glucagon/insulin ratio can be induced by treating fasted rats with antilipolytic drugs (e.g., with 3,5-dimethylpyrazole, 12 mg/kg body wt). These hormone changes are the physiologically appropriate response to a rapid decrease in free fatty acids and glucose plasma levels. Under this experimental condition, many vacuolated lysosomes can be observed at the electron microscopic level as early as 30 min and autophagic vacuoles are detectable in the liver cells 1 hr after the administration of the drug. By 1 hr and 45 min, vacuoles often contain recognizable peroxisomes. At the biochemical level, liver proteolysis in vitro is increased significantly. Very interestingly, changes in peroxisomal (but not mitochondrial or reticulum or cytosolic) enzyme activities are detected that are preventable by the administration of glutamine (i.e., of an inhibitor of proteolysis in vivo) but not by an isocaloric amount of glycine or alanine. It is concluded that the administration of antilipolytic agents to fasted animals may provide a convenient (i.e., an inexpensive, highly reproducible and timable) physiologic model to study hormone-induced autophagy in liver cells.
Exp Mol Pathol 1987 Feb
PMID:Increased degradation in rat liver induced by antilipolytic agents: a model for studying autophagy and protein degradation in liver? 354 50

This study investigated the modulatory effects of forskolin, phorbol 12-myristate 13-acetate (PMA) and arginine on pancreatic glucagon secretion in response to changes in glucose concentrations. Glucose, on its own (0, 5, 9 and 18 mM), did not modify glucagon secretion from A cell-rich isolated rat islets of Langerhans. In the presence of 20 microM forskolin, glucagon release was stimulated dose-dependently on lowering the external glucose concentration to 0 mM. Sensitivity to glucose was achieved in the presence of either PMA or arginine; both agents also significantly enhanced glucagon release at all glucose concentrations tested. The response of the B cells in these experiments were as expected from the available literature. These results indicate that the endogenous rate of glucagon secretion in the isolated islet preparation was minimal and was insensitive to glucose, sensitivity of the A cells to glucose could be restored by either arginine or agents which alter the concentration or activity of proposed cellular second messengers.
Mol Cell Endocrinol 1986 Dec
PMID:Restoration of the A cell response to glucose in isolated rat islets of Langerhans. 354 31

The state of differentiation of various neoplastic cell lines is inversely correlated with the rate of cellular growth. To delineate the changes in hormone gene expression associated with an induced decrease in the growth rate of rat insulinoma cells, we studied the effects of sodium butyrate on the expression of the genes encoding insulin, glucagon, and angiotensinogen. Sodium butyrate inhibited cellular proliferation and decreased levels of c-myc mRNA. Concomitantly, steady-state levels of mRNAs encoding insulin and glucagon increased by 10- and 8.5-fold, respectively, as a result of a specific increase in the transcription of both genes. Sodium butyrate also inhibited angiotensinogen gene expression, which was ectopic in the insulinoma cells. These observations suggest that sodium butyrate induces a pattern of events leading to the differentiation of the rat insulinoma cells.
Mol Cell Biol 1987 Jan
PMID:Transcriptional regulation of genes encoding insulin, glucagon, and angiotensinogen by sodium butyrate in a rat islet cell line. 355 Apr 24

Hormonal control of glucose production and of L-pyruvate kinase activity has been measured in isolated liver cells from fed control and thyroidectomized rats. In hypothyroid rats, sensitivity to isoproterenol as measured by these parameters was increased: the apparent K0.5 for isoproterenol-induced stimulation of glucose production decreased from 8.0 +/- 3 X 10(-6) M in control rats to 2.0 +/- 0.2 X 10(-8) M in hypothyroid rats (P less than 0.001) and the apparent K0.5 for inhibition of L-pyruvate kinase was 5 +/- 2 X 10(-7) M vs. 7 +/- 2 X 10(-9) M (P less than 0.001) in control and thyroidectomized rats, respectively. Utilisation of specific adrenergic antagonists confirmed increased beta-adrenergic responsiveness in hypothyroid rats. This phenomenon was not reversed by 3 days of T3 treatment (10 micrograms/100 g body weight). Sensitivity to the alpha-agonist was unchanged by thyroid status. Stimulation of glucose production and inhibition of L-pyruvate kinase activity by glucagon and their reversal by insulin were not affected by hypothyroidism. The dose-response curve to vasopressin and its maximal effect measured on stimulation of glucose production were unchanged in thyroidectomized rats. Thus, hypothyroidism produces a specific enhancement of liver beta-adrenergic responsiveness without affecting sensitivity to glucagon, insulin and vasopressin.
Mol Cell Endocrinol 1987 Apr
PMID:Hormonal control of glucose production and pyruvate kinase activity in isolated rat liver cells: influence of hypothyroidism. 356 54

The effect of glucose concentrations and hormones on glucose consumption, lactate, pyruvate, sorbitol and fructose formation of porcine aortic endothelial cells and human umbilical vein endothelial cells has been investigated. Endothelial cells have a high glycolytic activity which is saturated far below physiologic blood glucose levels (KM apparent less than 1 mmol/l). Glucocorticoids reduce glucose catabolism as a function of their concentration. Insulin, adrenaline, triiodothyronine and glucagon do not influence glucose consumption. Studies with the non-metabolizable analogue 3-O-methyl-D-glucose revealed that glucocorticoids slow down glucose transport into the endothelial cell. The passage of glucose through the cell membrane is the rate-limiting step of glucose utilization. Consequently, the intracellular glucose level is independent of the ambient glucose concentration and endothelial cells do not accumulate sorbitol under hyperglycaemic conditions since the affinity of aldose reductase for glucose is low.
Mol Cell Endocrinol 1985 Dec
PMID:Endothelial plasma membrane is a glucocorticoid-regulated barrier for the uptake of glucose into the cell. 390 87

Hepatocytes isolated from glucagon-treated rats contain stimulated System A activity. If these cells are placed in primary culture, the enhanced transport decays rapidly provided the culture medium contains substrate amino acids. This amino acid-dependent inactivation can be composed of trans-inhibition (protein synthesis-independent), repression (protein synthesis-dependent), or both depending on the particular substrate tested. Repression was most prominently observed with a group of small neutral amino acids that are commonly found in proteins. A strong trans-inhibition response was induced by a variety of amino acid analogs. Amino acids showing no reactivity with System A produced neither trans-inhibition nor repression. Repression of System A activity in culture was blocked by inhibitors of both RNA and protein synthesis. In contrast to inhibitors of RNA biosynthesis such as actinomycin and alpha-amanitin, inhibitors of poly(A) polymerase (cordycepin and adenine-9-beta-D-arabinopyranoside) did not prevent the inactivation of the transport activity. These results demonstrate that both the stimulation of activity and the turnover of the hepatic System A activity are controlled at the transcriptional level.
Mol Cell Endocrinol 1985 Nov
PMID:Amino acid-dependent inactivation of glucagon-induced System A transport activity in cultured rat hepatocytes. 406 25

Hepatic plasma membranes of female obese mice C57 BL-6 orl ob/ob (ob/ob mice) completely lack vasopressin (VP) receptors of the V1 type whereas kidney VP receptors are normally expressed and functionally coupled to adenylate cyclase. To discover if these alterations are linked to a genetic defect of the V1 receptor, we have studied the binding of VP on liver and kidney membranes of two other models, female diabetic mice C57 BL-6 orl db/db (db/db mice) and female Zucker rats Fatty/orl fa/fa (fa/fa rats), which exhibit different temporal pattern of obesity, hyperinsulinemia and insulin resistance. In addition, since VP is known to exert its vascular response through stimulation of V1 receptors, we have studied the reactivity of VP of isolated tail artery in the three different models, ob/ob and db/db mice and fa/fa rats, and in their respective controls. In all cases, VP kidney receptors and VP vascular reactivity are normal. db/db mice exhibit a marked decrease in hepatic VP receptors whereas a 50% decrease was observed in 32 week fa/fa rats. Angiotensin II and prazosin binding sites are still present as well as the adenylate cyclase response to glucagon. These results suggest that the specific alteration in liver VP receptors is not related to a defect in V1 receptor genetic expression but is specific for liver and appears to parallel the level of hyperinsulinemia and/or insulin resistance.
Mol Cell Endocrinol 1984 Dec
PMID:Reduction in hepatic but not in renal and vascular vasopressin receptor number in hyperinsulinemic mice and rats. 609 84

Number and affinity constant of low affinity binding sites of insulin and glucagon to isolated hepatocytes decreased when the cells were incubated with Escherichia coli 0111:B4 lipopolysaccharide. This effect agrees with a non-specific binding of lipopolysaccharide to hepatocytes, similar to the well-recognized non-specific binding of albumin. Also, binding of different lectins to their glycoprotein receptors did not affect the [14C]lipopolysaccharide interaction with the cell membrane surface. Endotoxin depresses gluconeogenesis from lactate when the precursor was incubated with the cells for short time intervals. The longer the preincubation interval with lipopolysaccharide, the higher the inhibition of gluconeogenesis in the absence and in the presence of glucagon. The effect of endotoxin was also studied on the glucagon-induced synthesis of cyclic AMP and the glucagon binding. Levels of cyclic AMP and hormone binding decreased with increasing both endotoxin concentrations and preincubation intervals at which cells were in contact with endotoxin.
Mol Cell Biochem 1984 Nov
PMID:Effect of Escherichia coli lipopolysaccharide on the glucagon and insulin binding to isolated rat hepatocytes. 609 7

Somatostatin has been shown to inhibit the release of various polypeptide hormones including insulin, glucagon, gastrin, thyroid stimulating hormone, and growth hormone. The mechanism by which somatostatin inhibits the release of these various polypeptide hormones has not been fully elucidated. It has been reported that somatostatin increases the level of the second messenger cyclic GMP in rat brain and in the anterior pituitary gland. The present investigation was designed to determine if these responses seen in the anterior pituitary gland and brain were due to activation of guanylate cyclase [GTP-pyrophosphate lyase (cyclizing), E.C.4.6.1.2.], the enzyme that catalyzes the formation of cyclic GMP. Somatostatin at a concentration of 2 pM enhanced guanylate cyclase activity two-fold in rat cerebrum and anterior pituitary gland. This enhancement of guanylate cyclase activity was also seen in rat liver, pancreas, stomach, and small intestine at the same concentration of somatostatin. Increasing the concentration of somatostatin to 20 microM, caused a marked inhibition of guanylate cyclase activity in all these tissues. Dose-reponse curves done on gastric guanylate cyclase activity revealed that over a concentration range of 2 pM to 0.2 microM, somatostatin had a stimulatory effect on guanylate cyclase activity while at concentrations above 10 microM somatostatin was inhibitory to guanylate cyclase activity. The biphasic pattern of enhancement of guanylate cyclase activity at lower concentrations of somatostatin and inhibition at higher concentrations may help to explain some of the discrepancies seen with previous investigations with somatostatin, hormone release, and cyclic nucleotide metabolism.
Mol Cell Biochem 1980 Nov 20
PMID:The interrelationship of somatostatin and guanylate cyclase activity. 611 Jan 70


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