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

Infusion of diazoxide (16.5 mg./kg. in 10 minutes) into normal unanesthetized dogs resulted in a prompt hyperglycemia due to increased hepatic glucose production as measured with a 3-3H-glucose primer-infusion technique. Plasma insulin and glucagon were decreased. Glucose uptake failed to increase. Diazoxide administration during period of alpha adrenergic receptor blockade with phentolamine still caused hyperglycemia and increased glucose production. Glucose uptake was inhibited despite adequate plasma insulin. Infusion of somatostatin along with insulin prevented the effects of diazoxide on plasma glucose and glucose production. It is concluded that diazoxide hyperglycemia is not due solely to decreased insulin secretion or increased epinephrine secretion and that glucagon is not a contributory factor. Diazoxide may act directly to increase glucose production and inhibit glucose uptake. Somatostatin appears capable of blocking the effect of diazoxide on glucose production by an unknown mechanism.
 ...
PMID:On the mechanism of diazoxide-induced hyperglycemia. 90 62

Somatostatin inhibition of growth hormone (GH) secretion from adenohypophysis cells in culture was antagonized by the antidiabetic sulfonylurea glipizide (K0.5 = 10 +/- 5 nM). Although all cells that hyperpolarize with somatostatin have ATP-sensitive K+ channels, the antagonistic actions of the hormone and of the antidiabetic drug are due to effects on different types of K+ channels. Diazoxide, an opener of ATP-sensitive K+ channels, abolished the increase of intracellular Ca2+ provoked by growth hormone releasing factor (GRF) and induced inhibition of GRF stimulated GH secretion (K0.5 = 138 microM). This inhibition by diazoxide was largely suppressed by glipizide which blocked the ATP-sensitive K+ channels opened by diazoxide. In summary, hormonal activation of GH secretion is inhibited by openers of ATP-sensitive K+ channels, while hormonal inhibition of GH secretion is suppressed by blockers of ATP-sensitive K+ channels.
 ...
PMID:Effectors of ATP-sensitive K+ channels inhibit the regulatory effects of somatostatin and GH-releasing factor on growth hormone secretion. 135 34

The sulfonylurea glibenclamide, which is known to block ATP-sensitive potassium channels, increases, in a dose-dependent manner, the release of PRL from MMQ pituitary cells. Glibenclamide does not reduce the dopaminergic inhibition of forskolin-stimulated PRL secretion; conversely it almost completely abolishes the inhibitory effect of somatostatin (SRIF) on this parameter. The sulfonylurea dose dependently increases basal [Ca++]i, without affecting the increase in [Ca++]i induced by high concentrations of extracellular potassium. Glibenclamide does not modify dopamine-induced [Ca++]i reduction, whereas it abolishes the inhibitory effect of SRIF on basal [Ca++]i. In the presence of diazoxide, an opener of ATP-sensitive potassium channels, which lowers basal [Ca++]i, dopamine still reduces [Ca++]i whereas SRIF does not induce a further decrease. Glibenclamide induces the depolarization of the cell membrane and prevents the SRIF-evoked hyperpolarization. The hyperpolarization of the cell membrane induced by dopamine is not modified by glibenclamide. Diazoxide induces a cell membrane hyperpolarization that is enhanced by dopamine but not by SRIF. Finally, glibenclamide does not affect basal and stimulated adenylate cyclase activity. In conclusion, our findings show that, in MMQ cells, glibenclamide stimulates PRL release, suggesting an involvement of ATP-sensitive potassium channels in the regulation of PRL secretion. The reversal by glibenclamide of the effects of SRIF on calcium homeostasis, membrane potential, and PRL release suggests that this type of potassium channel participates to the somatostatinergic inhibition of PRL secretion. Conversely, we found that glibenclamide does not modify the dopaminergic inhibition of PRL secretion and second messenger systems, suggesting that ATP-sensitive potassium channels may not be involved in the inhibitory effect of dopamine on PRL release.
 ...
PMID:Dopamine and somatostatin inhibition of prolactin secretion from MMQ pituitary cells: role of adenosine triphosphate-sensitive potassium channels. 135 54

In CA3 hippocampal neurons of the rat, brief anoxic episodes produce a depolarization which is probably due to a synaptic release of glutamate. Diazoxide, an activator of ATP-sensitive K+ channels (K+ ATP), blocks the anoxic depolarization and has no effect in control oxygenated artificial cerebrospinal fluid. The hormone somatostatin which activates K+ ATP channels in the pancreas also reduces the anoxic depolarization in CA3 neurons. We suggest that drugs that open K+ ATP channels may constitute a novel approach to selectivity reducing the deleterious effects of excessive release of glutamate during anoxia without producing a generalized blockade of glutamatergic synaptic transmission.
 ...
PMID:Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons. 197 42

The effect of a new benzothiadiazine derivative, LN 5330, was studied on insulin secretion from isolated perfused rat pancreas. LN 5330 (1 mg/l to 125mg/l) induced an inhibition of insulin secretion evoked by glucose 1.5 g/l. In all cases the inhibition recorded during the infusion was followed by an increase in insulin secretion after stopping the infusion. This increase was biphasic with LN 5330 at 1, 3, 5 and 15 mg/l. The insulin increase as well as the insulin decrease were dose-related but the additional amount of insulin released after stopping LN 5330 was higher than the amount of insulin which was not released during the infusion of LN 5330. Diazoxide and somatostatin were infused at concentrations which induced an inhibitory effect similar to that obtained with LN 5330 (15 mg/l). When diazoxide infusion was stopped, only a very transient overshoot appeared and after somatostatin infusion insulin secretion progressively returned to reference value. It is concluded that LN 5330 by inducing inhibition and secondary increase of insulin output might be a valuable tool for studying the mechanisms involved in insulin secretion.
 ...
PMID:Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion. 611 62

After mentioning insulin deficiency diabetes in animals produced by drugs such as Alloxan, Diazoxide or Streptozotocin only drugs are discussed, which are used in elderly patients and may either provoke diabetes mellitus (or temporary hyperglycemia) or may change the clinical course of diabetes. In the first group endocrine products such as corticosteroids, estrogens, somatotrophic hormone, thyroid hormone, glucagon, somatostatin, catecholamines and hormones with anabolic effects are listed. The second group comprises saluretics, salicylates, amphetamines, pentamidine, nicotinic acid and its derivatives, beta-receptor blockers and finally laxatives. Hypopotassemia alone can also be the cause of hyperglycemia. Speaking of the sulfonylureapreparations, their interaction with alcohol, with phenylbutazone, with some sulfonamides and the effect of the sulfonylureas on peripheric insulin-receptors is discussed. In case of severe diabetic vascular disease the use of anticoagulants may lead to hemorrhages. If such an hemorrhage occurs in the eyes, it may lead to blindness. In diabetic nephropathy the use of phenacetine and its derivatives should be substituted by another medication. This review is not at all complete but should only show some of the problems in the treatment of elderly diabetic patients.
 ...
PMID:[Iatrogenic diabetes mellitus (side effects and interactions of drugs during clinical diabetes mellitus (author's transl)]. 612 38

We studied the effect of the ionophere A 23187 and of phosphodiesterase inhibitors and activators (Theophylline, Pentoxiphylline and Imidazol) on insulin secretion and on the pool of free tubulin in rat pancreas in the presence of somatostatin and diazoxide. The results suggest that: 1. The inhibitory effect of somatostatin on insulin secretion does not seem to be related mainly to an inhibition of cAMP production. The decrease in calcium translocation induced by somatostatin could inhibit the cAMP participation in the mechanism of hormonal secretion. 2. Somatostatin seems to inhibit the movement of calcium towards the cytoplasm from outside and from within the cell. Diazoxide seems to inhibit only the entrance of calcium from outside the cell but does not seem to inhibit the entrance determined by theophylline and pentoxiphylline from intracellular compartments. 3. Arginine glucose stimulation in the presence of A 23187-induced calcium translocation is able to determine insulin secretion although cAMP degradation is increased by imidazol. 4. Somatostatin and diazoxide inhibit pancreatic tubulin polimerization; however, the effect seem to be indirect and related to the inhibition of calcium translocation determined by both substances.
 ...
PMID:A comparative study of two insulin secretion inhibitors: somatostatin and diazoxide. 612 27

Somatostatin (SRIF) acts as a physiological regulator of insulin and glucagon secretion. This study explored whether alterations in SRIF secretion and activity in perifused pancreas from spontaneously diabetic mice (C57BL/KsJ-db/db) could be correlated with hypersecretion of insulin by the beta-cells. SRIF release upon stimulation with 27.5 mM glucose was biphasic in controls, whereas a first phase peak was absent in 30-to 90-day-old diabetic mice (db/db). Twelve- to 28-day-old db/db mice showed two distinct patterns compared to controls: biphasic hypersecretion in the 12- to 20-day-old group compared to normal secretion in the 22- to 28-day-old group. Basal SRIF secretion showed a tendency to be elevated above controls in some of the db/db age groups, but the difference was not statistically significant. Insulin release from control pancreases was biphasic, whereas in db/db mice, basal hypersecretion, absence of the first peak, and second phase hypersecretion were observed. beta-Cell sensitivity to the inhibitory effect of SRIF was diminished in db/db mice aged 12-90 days. Diazoxide, on the contrary, inhibited insulin secretion from the pancreas of diabetic and normal mice to the same extent. The results suggest that altered secretion of and response to SRIF in C57BL/KsJ-db/db mice might provide an explanation for the anomalies in insulin secretion in the first stages of this type of diabetic syndrome.
 ...
PMID:A temporal study of somatostatin secretion and its inhibitory effect in genetically diabetic mice (C57BL/KsJ-db/db). 613 72

We studied the release of insulin, glucagon, and somatostatin in response to glucose, glyceraldehyde (GA), and alpha-ketoisocaproate (KIC) from rat kidneys containing transplanted insulinomas. Kidneys were perfused about 11 wk after transplantation when the plasma glucose concentration of the fed animals had decreased from 180 +/- 7 to 95.1 +/- 9.9 mg/dl and plasma insulin concentrations had increased from 2.6 +/- 0.5 to 14.2 +/- 2.0 ng/ml. The insulin content of the tumor-containing kidney ranged from 40 to 679 micrograms; the glucagon and somatostatin concentrations ranged from undetectable levels to 3.7 micrograms and 248 ng, respectively. The average response to 30 mM glucose and 10 mM GA was a four- to fivefold increase in insulin secretion, whereas 30 mM KIC caused a 16- to 28-fold increase. In vitro stimulation of the insulinoma with 30 mM glucose primed the beta-cell response to a second stimulus following a short rest period. Cytochalasin B did not enhance this primed glucose response. Diazoxide inhibited glucose, GA, and KIC-stimulated insulin release. Glucose, GA, and KIC stimulated glucagon release in 2 of 17 insulinomas studied here. Somatostatin release was not seen in any of the experiments. These findings show that this islet cell tumor transplanted under the kidney capsule releases insulin in response to physiologic and model fuel substances. Thus, this particular transplantable tumor offers an opportunity to study the biochemistry and biophysics that underlie fuel-stimulated insulin release.
 ...
PMID:Fuel-induced insulin release in vitro from insulinomas transplanted into the rat kidney. 614 Jan 99

The neonatal disorder persistent hyperinsulinemic hypoglycemia of infancy (PHHI) arises as the result of mutations in the subunits that form the ATP-sensitive potassium (KATP) channel in pancreatic beta cells, leading to insulin hypersecretion. Diazoxide (a specific KATP channel agonist in normal beta cells) and somatostatin (octreotide) are the mainstay of medical treatment for the condition. To investigate the mechanism of action of these agents in PHHI beta cells that lack KATP currents, we applied patch clamp techniques to insulin-secreting cells isolated from seven patients with PHHI. Five patients showed favorable responses to medical therapy, and two were refractory. Our data reveal, in drug-responsive patients, that a novel ion channel is modulated by diazoxide and somatostatin, leading to termination of the spontaneous electrical events that underlie insulin hypersecretion. The drug-resistant patients, both of whom carried a mutation in one of the genes that encode KATP channel subunits, also lacked this novel K+ channel. There were no effects of diazoxide and somatostatin on beta cell function in vitro. These findings elucidate for the first time the mechanisms of action of diazoxide and somatostatin in infants with PHHI in whom KATP channels are absent, and provide a rationale for development of new therapeutic opportunities by K+ channel manipulation in PHHI treatment.
 ...
PMID:Therapy for persistent hyperinsulinemic hypoglycemia of infancy. Understanding the responsiveness of beta cells to diazoxide and somatostatin. 931 91


1 2 Next >>