Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic somatostatin (SRIF) secretion was examined using the RIA described in earlier paper. Ten isolated rat pancreatic islets were incubated for 30 min in 1 ml Krebs-Ringer bicarbonate buffer. Glucose (5.6 mM) caused a small but significant increase of SRIF secretion. The maximal secretion rate was observed at 16.7 mM glucose, and the half-maximal rate was seen at about 9.7 mM. Islets preincubated with 16.7 mM glucose released higher levels of SRIF and insulin during the subsequent incubation with 16.7 mM glucose than did islets preincubated with 2.8 mM glucose. Glucose-induced SRIF secretion was suppressed by epinephrine, but beta-adrenergic stimulation (epinephrine and phentolamine) produced an increase in SRIF secretion. Islets taken from rats 2 days after streptozotocin administration released minimal amounts of insulin. Basal and glucose-induced SRIF secretion from these islets, which had relatively unchanged SRIF contents and D cell numbers, equaled SRIF secretion from control rat islets. Islets taken from rats 6 weeks after streptozotocin administration, however, had increased SRIF content and D cell numbers, and they oversecreted SRIF. We conclude that pancreatic SRIF secretion can be induced by glucose and modulated by catecholamines and preexposure to high glucose, and the duration and severity of diabetes may be an important determinant of the changes in pancreatic D cell structure and function.
 ...
PMID:Effect of glucose on somatostatin secretion from isolated pancreatic islets of normal and streptozotocin-diabetic rats. 611 54

The widespread role of somatostatin (SRIF) as a mediator of function in the brain and gut has stimulated interest in it mechanism of action. We have examined the mode of action of SRIF in stimulus-secretion coupling in the pancreatic islet beta-cell to determine whether SRIF antagonizes the glucose-induced decrease in K+ permeability (PK). The influence of SRIF on 86Rb fluxes and insulin release in cultured rat islet cells, and also the electrical events recorded from cultured islets and microdissected mouse islets, was examined. In cultured islets, 100 ng/ml SRIF in the presence of 16.7 mM glucose inhibited the incidence of spike activity and evoked hyperpolarization. This effect was counteracted by 0.1 mM quinine and 20 mM tetraethylammonium (TEA), drugs that inhibit the Ca2+-sensitive or voltage-sensitive increase in PK, respectively. These agents also counteracted the inhibitory influence of SRIF on glucose-induced insulin release in cultured islets. SRIF disrupted the typical glucose-induced oscillatory pattern of electrical activity (burst activity) during continuous microelectrode recordings in mouse beta-cells, resulting in a transient 5mV hyperpolarization and a decrease in the frequency of generation of burst activity. The presence of 20 mm TEA prevented the influence of SRIF on the electrical activity. SRIF had no effect on the accumulation of 86Rb into islet cells obtained in the presence of 16.7 mM glucose. However, SRIF enhanced the rate of 86Rb efflux from cells exposed to glucose. SRIF-induced enhancement of 86Rb efflux was antagonized by TEA or quinine. These results indicate that SRIF may activate PK as its primary mode of action, an event that may be sufficient to reduce the accumulation of intracellular Ca2+ thereby disrupting glucose-induced stimulus-secretion coupling.
Diabetes 1981 Oct
PMID:Somatostatin: mechanism of action in pancreatic islet beta-cells. 611 84

Alterations in the somatostatin (SRIF)-, insulin- and glucagon-containing cells were examined in two strains of spontaneously diabetic mice, KK and newly inbred non-obese diabetic (NOD) mice, using radioimmunoassay and immunohistochemical methods. The total pancreatic content and concentration of SRIF was decreased in male KK mice compared to their male controls aged 12-18 weeks. These results were consistent with the immunohistochemical findings. Pancreatic glucagon concentration and number of glucagon-containing cells were also decreased in KK mice, but pancreatic insulin concentrations were increased in KK mice. On the other hand, NOD mice aged 12-38 weeks within 15 days after onset of diabetes had increased concentrations of pancreatic SRIF. The pancreatic islets in NOD mice were decreased both in number and in size and were characterized by lymphocyte infiltration. SRIF-containing cells occupied the major part of the endocrine cells of the islets. Insulin-containing cells significantly decreased in number, but the number of glucagon-containing cells was fairly well preserved. These results and previous work concerning obob and dbdb mice indicate a parallel relationship between pancreatic SRIF and glucagon. The pancreatic glucagon thus as well as the pancreatic insulin may be an important determinant of pancreatic SRIF concentration in these diabetic animals.
 ...
PMID:Pancreatic somatostatin contents in spontaneously diabetic KK and non-obese diabetic (NOD) mice. 612 26

Somatostatin-like immunoreactivity (SLI) from dog and rat plasma eluted from Biogel P-6 columns as three distinct peaks. A large-molecular-weight peak was present in the void volume of the column, an intermediate-sized peak (SLI28) coeluted with synthetic somatostatin 28 (S-28), and a small-molecular-weight peak (SLI14) coeluted with SRIF. Material from the SLI28 peak diluted in parallel to the S-28 standard in the radioimmunoassay and behaved identically to S-28 on high pressure liquid chromatography (HPLC). Levels of SLI28 in the portal vein were consistently greater than the simultaneously measured peripheral levels (portal peripheral ratio 2.2 +/- 0.2). Venous samples drawn from multiple sites suggested that SLI28 is segregated by the duodenum and/or pancreas and the intestine. This data is consistent with the possibility that S-28 is a hormone distinct from SRIF.
Diabetes 1982 May
PMID:Evidence for the presence of somatostatin 28 in plasma. 613 21

The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14. Soluble insulin was infused continuously overnight on one occasion and on another occasion the same quantity was given in pulses of 2-min duration with a gap of 11 min. The mean plasma glucose concentrations were lower when pulsed insulin was given [mean for the last hour: 4.66 +/- 0.08 mmol/L (+/- SEM) versus 5.53 +/- 0.06 mmol/L (+/- SEM) for steady infusion], diverging significantly (P less than 0.05 paired t test) 7 h after the start of the study. The specific binding of 125I(A14)mono-iodo-insulin to monocytes was greater after pulsed insulin (2.9% with pulsed versus 2.4% with steadily infused insulin at tracer-only point; P less than 0.02 paired t test). Thus, intravenous insulin has greater hypoglycemic effect when pulsed, possibly mediated by greater insulin receptor binding.
Diabetes 1983 Jul
PMID:Pulsatile insulin has greater hypoglycemic effect than continuous delivery. 613 49

Addition of diet fiber to meals is reported to result in significant reduction of postprandial glucose levels in diabetic patients as well as in normal subjects. In the present study effect of guar intake (12 g) on plasma somatostatin-like immunoreactivity (SRIF-LI) was studied in non-insulin dependent diabetes (NIDDM) and in insulin-dependent diabetes (IDDM) to see if somatostatin plays a role in reducing postprandial glucose. In 6 of 7 normal controls plasma SRIF-LI increased and reached a maximum at 30 min after guar intake. In 5 of 7 NIDDM patients SRIF-LI reached a maximum at 90 min after guar intake, while in five IDDM patients SRIF-LI significantly decreased through 120 min after guar intake. These results suggest the possibility that guar induced somatostatin secretion contributes to reduction of postprandial glucose levels at least in NIDDM patients as well as in normal subjects, for somatostatin is reported to inhibit glucose uptake from gastrointestinal tract.
 ...
PMID:Effect of guar intake on plasma somatostatin-like immunoreactivity in diabetic patients. 613 60

The effects of streptozotocin-induced diabetes on pituitary growth hormone (GH) content and release from incubated pituitaries were investigated. Male rats were made diabetic by a single injection of streptozotocin (65 mg/kg) and sacrificed by decapitation 15 days later. Pituitary GH concentration was significantly reduced in streptozotocin diabetic rats as compared to that observed in control animals. The amount of GH released from hemipituitaries was also lower in diabetic rats than in controls. Kinetic characteristics of somatostatin (SRIF) inhibition of GH release were not affected by the treatment. These results suggest that the decrease in plasma GH observed by some investigators in streptozotocin diabetic rats is probably due to a deficiency in GH storage and/or synthesis rather than a change in the responsiveness of pituitary GH cells to SRIF.
 ...
PMID:Influence of streptozotocin-induced diabetes on growth hormone secretion in the rat. 613 72

Somatostatin-14 (S-14) and somatostatin-28 (S-28) circulate in normal portal plasma and are rapidly metabolized by the liver. In the present study we have investigated the hepatic clearance of the two peptides in insulinopenic diabetes using as a model spontaneously diabetic BB rats. Isolated livers from three groups of five nondiabetic, untreated diabetic, or insulin-treated diabetic animals were perfused with synthetic S-14 or S-28. The metabolism of the two peptides was monitored as S-14-like immunoreactivity by RIA using antibody R149 specific for the central segment of S-14, which detects S-14 and S-28 equally. The t1/2 and hepatic extraction of S-14 in untreated diabetic rats (25.9 +/- 2.6 min and 27.1 +/- 4.6%, respectively) were significantly different (P less than 0.01) compared with nondiabetic control values (13.3 +/- 1.1 min and 42.8 +/- 2.5%) and were normalized with insulin treatment (13.1 +/- 1.0 min and 42.0 +/- 2.3%). Similarly, the t1/2 of S-28 disappearance and the hepatic extraction of the peptide in untreated diabetic rats (62.1 +/- 1.8 min and 9.8 +/- 0.6%) were also significantly different (P less than 0.05) from nondiabetic control values (44.0 +/- 1.9 min and 13.7 +/- 1.6%) and were normalized with insulin treatment (47.2 +/- 2.0 min and 13.1 +/- 1.8%). Sephadex G-50 gel chromatography of media after S-28 perfusion showed two peaks of S-14-like immunoreactivity corresponding to S-28 and S-14. The extent of S-28 to S-14 conversion varied from 10% in 10-min perfusion samples to 30% in 60-min samples and was identical in normal and untreated diabetic rats. We conclude that 1) S-14 is metabolized more rapidly than S-28 by livers of both normal and diabetic rats; 2) the hepatic extraction of S-14 and S-28 is significantly impaired in insulin-deficient diabetic rats and normalized with insulin treatment; and 3) S-28 is significantly converted to S-14 equally in normal and diabetic rats.
 ...
PMID:Impaired hepatic metabolism of somatostatin-14 and somatostatin-28 in spontaneously diabetic BB rats. 614 81

The secretory responses of beta and delta cells were compared in the isolated, perfused, rat pancreas. Insulin release was stimulated 50-fold and somatostatin (SRIF) secretion twofold when the glucose concentration was increased from 100 mg/dl to 300 mg/dl. When islet cyclic AMP (cAMP) was raised by 3-isobutyl-1-methylxanthine (IBMX), the secretion of SRIF was stimulated in a glucose-dependent manner (300 mg/dl greater than 100 mg/dl greater than 25 mg/dl). As expected, insulin release was also potentiated in a similar fashion. A difference in the glucose dependency of the cAMP effect was seen at 25 mg/dl glucose, where 0.25 mM IBMX enhanced the release of SRIF but not that of insulin. In contrast, at 300 mg/dl glucose, IBMX caused a greater potentiation of insulin release than of SRIF release. The release of insulin, when expressed in absolute terms, was stimulated more markedly than that of SRIF under most conditions tested. However, the expression of total hormone released during 30 min of stimulation as a percentage of tissue hormone content allowed a different interpretation of the results. For example, 2.1% and 1.8% of tissue insulin and SRIF contents, respectively, was released during exposure to 300 mg/dl glucose. Surprisingly, under basal conditions (100 mg/dl glucose), 1.0% of total SRIF content was released during 30 min compared with the release of only 0.04% of insulin.
Diabetes 1981 Jan
PMID:Glucose and cyclic AMP as stimulators of somatostatin and insulin secretion from the isolated, perfused rat pancreas: a quantitative study. 616 86

It may now be possible to identify certain intracellular events that impact specifically on secretion-granule fusion to the plasma membrane or on granule lysis. Secretion vesicles in isolated rat islets appear to translocate somatostatin (SRIF) receptors from the Golgi apparatus to the plasma membrane. We have proposed that secretion granule fusion to the plasma membrane can be determined by measuring recruitment of SRIF receptors to the surface membrane. Granule lysis can be assessed by measuring insulin release. To activate cyclic AMP (cAMP)-dependent pathways, we employed isobutylmethylxanthine (IBMX, 400 microM), glucagon (10 microM), and forskolin (20 microM), a diterpene activator of adenylate cyclase. These agents evoked rapid release of insulin (from 0.41 +/- 0.02 to 1.88 +/- 0.02; 0.41 +/- 0.02 to 1.93 +/- 0.08; and 0.41 +/- 0.02 to 1.66 +/- 0.03 microU/islet/min, respectively, P less than 0.001). There was no concomitant recruitment of SRIF receptors. Somatostatin (10 micrograms/ml), which inhibits cAMP-stimulated protein phosphorylation, suppresses insulin release evoked by IBMX, glucagon, or forskolin (inhibition: 80, 75, or 82%, respectively). In contrast, trifluoperazine (10 microM), an inhibitor of calmodulin, did not suppress insulin release induced through cAMP-dependent pathways. Trifluoperazine suppresses glucose-induced insulin release and the recruitment of SRIF receptors to the surface membrane, suggesting the possible role of calmodulin in promoting secretion-granule fusion with the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Apr
PMID:Calmodulin and cyclic AMP. Possible different sites of action of these two regulatory agents in exocytotic hormone release. 620 Mar 77


<< Previous 1 2 3 4 5 6 7 Next >>