Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neonatal streptozocin (STZ) rat model of NIDDM has been previously found to have a markedly reduced insulin response to an acute increase in glucose concentration. We studied the effect of an acute reduction in glucose concentration on insulin and glucagon secretion in this model and contrasted the results with the effects of epinephrine and somatostatin using the in vitro isolated, perfused pancreas. The reduction in perfusate glucose concentration from 11.1 to 2.8 mM caused a rapid suppression of insulin release in the control rats, but had no inhibitory effect in the STZ group. Epinephrine (55 nM) and somatostatin (110 nM) caused similar decreases in insulin secretion in both groups. The glucose reduction also caused an increase in glucagon release in the controls, but had no effect in the STZ rats. Epinephrine, however, stimulated glucagon secretion in both groups in a similar fashion, and inhibition by somatostatin was also comparable. The baseline insulin and glucagon concentrations were enhanced in a separate series of experiments by the addition of arginine (5 mM) to the perfusate, and while the insulin and glucagon responses to the glucose reduction remained lost, appropriate inhibition of insulin secretion was demonstrated in the STZ rats with epinephrine. These data indicate that A- and B-cells in this rat model of NIDDM are selectively unresponsive to both increases and decreases in glucose concentration, while the responsiveness to nonglucose agents remains intact.
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PMID:Unresponsiveness to glucose in a streptozocin model of diabetes. Inappropriate insulin and glucagon responses to a reduction of glucose concentration. 286 Nov 28

In order to obtain an appropriate tissue model to study human diabetes we isolated islet cells from pancreata obtained from brain-dead, heart-beating kidney donor subjects by collagenase dispersion and tissue culture. The presence of viable islet cells was confirmed by both immunofluorescence staining and hormone release experiments. Insulin and somatostatin release were determined on culture day 3 or 4 when amylase measurements indicated an absence of functional exocrine cells. Glucose, alpha-ketoisocaproic acid, theophylline, glucagon, and tolbutamide each stimulated insulin release 2- to 3-fold and somatostatin release 1.5- to 2-fold. Epinephrine and somatostatin both inhibited glucose-stimulated insulin release. Successful subculture of islet cells was achieved after dispersion of primary cultures with dispase. Subcultured islet cells released insulin into the medium during a subsequent 8-day period and when challenged with glucose responded with a 1.6-fold increase in insulin output. Cells cultured on glass coverslips were used to detect, by indirect immunofluorescence, islet cell surface antibodies (ICSA) in the sera of patients with insulin-dependent diabetes mellitus. Of 15 sera from patients with newly diagnosed insulin-dependent diabetes mellitus 9 were ICSA positive, whereas all of 10 control sera were negative; in contrast, using rat insulinoma cells only 4 diabetic sera were positive, as well as 2 control sera. These findings demonstrate the functional viability of adult human islet cells in primary and secondary culture. Cultured human islet cells are a novel, sensitive, and specific system for detecting ICSA and for studying autoimmune effects, and provide a potential source of islet cells for transplantation.
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PMID:Adult human pancreatic islet cells in tissue culture: function and immunoreactivity. 286 82

The effect of chemical stimulation of the brain on glucoregulation was studied in anaesthetized rats. Adrenaline, noradrenaline, acetylcholine, dopamine and carbachol (5 X 10(-8) mol/microliter saline) were injected directly into the third cerebral ventricle and changes in hepatic venous plasma glucose, immunoreactive glucagon and insulin concentrations were studied. The injection of adrenaline and carbachol into the third cerebral ventricle resulted in a marked hyperglycaemia associated with increased immunoreactive glucagon. Adrenaline-induced hyperglycaemia was not affected by bilateral adrenalectomy, while carbachol-induced hyperglycaemia was completely inhibited by adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with adrenaline into the third cerebral ventricle did not influence adrenaline-induced hyperglycaemia, while carbachol-induced hyperglycaemia was inhibited by co-administration with somatostatin. These results suggest that adrenergic and cholinergic neurons in the central nervous system may increase hepatic glucose output by different mechanism.
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PMID:Central hyperglycaemic effect of adrenaline and carbachol. 286 11

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10-12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes. 286 46

A recently developed primary cell-culture system allows direct study of the cellular mechanisms regulating neurotensin secretion from intestinal mucosal cells. We now report the use of these methods to evaluate the modulation of neurotensin release by adrenergic, cholinergic, and peptidergic transmitters. Collagenase-dispersed canine ileal mucosal cells, enriched for neurotensinlike immunoreactivity (NTLI) by centrifugal elutriation, were maintained for 48 h on collagen-coated culture dishes. Epinephrine (0.01-100 microM) stimulated a dose-dependent increase increase in NTLI secretion. The NTLI response to epinephrine increase in NTLI secretion. The NTLI response to epinephrine was competitively inhibited by propranolol, producing a parallel rightward shift of the epinephrine dose-response curve. alpha-Adrenergic agonist methoxamine (10 microM) and clonidine (10 microM) did not alter basal NTLI secretion. Epinephrine stimulation was not significantly inhibited by the alpha-adrenergic antagonists prazosin (10 microM) or yohimbine (10 microM). The diterpene forskolin, an adenyl cyclase activator, increased NTLI release and had an additive effect on the response to epinephrine. In contrast to beta-adrenergic activation, carbachol and somatostatin produced a dose-dependent inhibition of epinephrine-stimulated NTLI release. At 100 microM carbachol, NTLI release was inhibited 68%, and this action was partially blocked by atropine (0.1 microM). Somatostatin (100 nM) produced a 96% inhibition that was not surmountable by 1 mM epinephrine. These data indicate that neurotensin release is stimulated by beta-adrenergic agonists and adenylate cyclase activation. Somatostatin and the muscarinic agonist carbachol directly inhibit NTLI release.
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PMID:Regulation of neurotensin release from canine enteric primary cell cultures. 286 96

The effect of chemical stimulation of the central nervous system was studied in anesthetized rats. (Bu)2 cAMP, cAMP, 5'-adenosine monophosphate (AMP), ATP, and (Bu)2 N6,O2-dibutyryl guanosine-3'5'-cyclic monophosphate sodium salt were injected directly into the third cerebral ventricle, and changes in hepatic venous plasma glucose, immunoreactive glucagon, and insulin concentrations were studied. The injection of (Bu)2cAMP (1 X 10(-8) to 5 X 10(-7) mol/microliter saline) into the third cerebral ventricle caused a dose-dependent hyperglycemia associated with increased immunoreactive glucagon. (Bu)2cAMP-induced hyperglycemia and hyperglucagonemia were inhibited by prior bilateral adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with (Bu)2cAMP (5 X 10(-7) mol) into the third cerebral ventricle abolished both (Bu)2cAMP-induced hyperglycemia and an increase of glucagon secretion. These results suggest that cAMP may act intracellularly within the central nervous system to increase hepatic glucose output, and this appears to depend on the adrenal gland. Epinephrine secreted from the adrenal gland may directly act on the liver or enhance glucagon secretion, which in turn increases hepatic glucose output.
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PMID:Increase in plasma glucose concentration after intracerebroventricular injection of N,O'-dibutyryl cyclic adenosine 3',5'-monophosphate. 287 22

Adrenal glands from embryonic day 11 (E-11) chicks were cryostat-sectioned, and it was determined that tyrosine hydroxylase-like immunoreactive (TLI) cells, somatostatin-like immunoreactive (SLI) cells, and methionine-enkephalin-like immunoreactive (ELI) cells occupied chromaffin regions of the gland. Similar age adrenals were dissociated, and the cells were cultured under serum-free conditions. Cultured TLI cells, ELI cells, and SLI cells were characterized according to cell size, cell number, and neurite formation. ELI and SLI cells composed two largely separate populations, with SLI cells tending to have larger cell areas, to be more numerous, and to be less likely to form neurites than ELI cells. The population of TLI cells, although unique in itself, was diverse and numerous enough to include all or portions of the neuropeptide-immunoreactive populations. Neurites of some cells from each of the above populations were strongly immunoreactive for alpha neurofilament protein, and for NAPA73 neurofilament-associated protein. However, neurites could also be observed in all populations that showed poor immunoreactivity for these cytoskeletal proteins. Exogenously added NGF significantly increased neurite-like process formation among TLI and ELI cells, but not among SLI cells. Reductions in the number of neurite-like processes following treatment with anti-nerve growth factor (NGF) were not significant for any of the populations. However, if shorter and broader process were included, anti-NGF caused a significant reduction in total cell processes among TLI and ELI cells. Anti-NGF inhibition of process formation among ELI cells could be reversed with exogenous NGF. Neither NGF or anti-NGF treatments showed a significant effect on cell numbers among TLI and ELI populations. The implications are that a compound of antigenic and physiological similarity to mouse salivary NGF is made by embryonic chick adrenal cells in culture, but the effects of NGF do not appear to be the same for all neural-crest-derived cells from the adrenal, and greater heterogeneity of phenotypes may exist among chromaffin cells than has previously been accepted. Some questions are also raised concerning the neurite-like nature of processes formed by some chromaffin cells in vitro.
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PMID:Chromaffin cell heterogeneity of process formation and neuropeptide content under control and nerve growth factor-altered conditions in cultures of chick embryonic adrenal gland. 287 7

Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress.
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PMID:Nutritional status and endocrine response to hemorrhage. 287 24

The regulation of TSH release in man was investigated using cell cultures derived from human pituitaries obtained within 24 h of accidental death. TRH stimulated TSH release in a dose-dependent manner. The ED50 was 2.9 +/- 0.6 (+/- SEM) nmol/L, similar to that reported for rat pituitary cell cultures. The release of TSH was calcium dependent, since the calcium channel antagonist verapamil inhibited TRH-stimulated TSH release, and the calcium ionophore A23187 stimulated TSH release. 12-O-Tetradecanoyl-phorbol-13-acetate stimulated TSH secretion, while dibuytryl cAMP had no effect. Epinephrine and serotonin stimulated TSH release, and dopamine and somatostatin inhibited TRH-stimulated TSH release. These findings have directly demonstrated that the regulation of TSH secretion by hypothalamic neuropeptides and biogenic amines in the human pituitary is similar to that in the rat. The development of a tissue culture system to study thyrotrophs from postmortem human pituitaries provides the means for detailed studies of the regulation of TSH secretion in man.
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PMID:Neuroendocrine regulation of thyrotropin release in cultured human pituitary cells. 289 Jun 53

Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site.
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PMID:Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells. 290 2


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