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)

Nitric oxide has recently been implicated as the effector molecule that mediates IL-1 beta-induced inhibition of glucose-stimulated insulin secretion and beta-cell specific destruction. The pancreatic islet represents a heterogeneous cell population containing both endocrine cells (beta-[insulin], alpha-]glucagon], gamma[somatostatin], and PP-[polypeptide] secreting cells) and non-endocrine cells (fibroblast, macrophage, endothelial, and dendritic cells). The purpose of this investigation was to determine if the beta-cell, which is selectively destroyed during insulin-dependent diabetes mellitus, is both a source of IL-1 beta-induced nitric oxide production and also a site of action of this free radical. Pretreatment of beta-cells, purified by FACS with IL-1 beta results in a 40% inhibition of glucose-stimulated insulin secretion that is prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (NMMA). IL-1 beta induces the formation of nitric oxide by purified beta-cells as evidenced by the accumulation of cGMP, which is blocked by NMMA. IL-1 beta also induces the accumulation of cGMP by the insulinoma cell line Rin-m5F, and both NMMA as well as the protein synthesis inhibitor cycloheximide prevent this cGMP accumulation. Iron-sulfur proteins appear to be intracellular targets of nitric oxide. IL-1 beta induces the formation of an iron-dinitrosyl complex by Rin-m5F cells indicating that nitric oxide mediates the destruction of iron-sulfur clusters of iron containing enzymes. This is further demonstrated by IL-1 beta-induced inhibition of glucose oxidation by purified beta-cells, mitochondrial aconitase activity of dispersed islet cells, and mitochondrial aconitase activity of Rin-m5F cells, all of which are prevented by NMMA. IL-1 beta does not appear to affect FACS-purified alpha-cell metabolic activity or intracellular cGMP levels, suggesting that IL-1 beta does not exert any effect on alpha-cells. These results demonstrate that the islet beta-cell is a source of IL-1 beta-induced nitric oxide production, and that beta-cell mitochondrial iron-sulfur containing enzymes are one site of action of nitric oxide.
 ...
PMID:Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. 133 75

1. The effect of the long-acting somatostatin analogue SMS-201995 on diabetes control was assessed in 6 insulin-dependent diabetic patients (3 men and 3 women aged 19-38 years). 2. Plasma glucose and triglyceride profiles were obtained on 4 consecutive days, from 8:00 a.m. to 2:00 p.m. On the first 2 days the patients received their usual dose of insulin and ate at 8:00 a.m. and at noon. On the third and fourth days they received 1/3 of their usual insulin dose together with 100 micrograms SMS-201995 injected subcutaneously. 3. Postprandial glucose and triglyceride increases were blunted during the 360 min of observation on both days after SMS-201995 administration. The areas under the glucose-time plots fell from 23.72 +/- 12.29 (mean +/- SD) to 7.98 +/- 14.26 (P < 0.05) and the areas under the triglyceride-time plots from 10.51 +/- 9.01 to -3.15 +/- 4.30 g.min.dl-1 (P < 0.01). 4. No adverse reactions were observed after SMS-201995 administration for 2 days. 5. We conclude that administration of the somatostatin analogue SMS-201995 may be beneficial for insulin-dependent diabetic patients.
 ...
PMID:Acute effect of the somatostatin analogue SMS-201995 on plasma glucose and triglycerides in insulin-dependent diabetic patients. 134 35

In a prospective clinical-experimental study, 15 patients with chronic pancreatitis operated consecutively due to severe pain were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th postoperative day, and three months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, somatostatin, and pancreatic polypeptide were determined. As indicated by the k-value, glucose tolerance improved postoperatively in 11 patients; two patients showed no change, and one patient was worse. Only one patient developed evident diabetes mellitus immediately postoperatively. The pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (2p less than 0.01). Duodenum-preserving pancreas head resection led to improvement of the glucose tolerance in the majority of patients; a deterioration was observed only in two cases.
 ...
PMID:[The effect of duodenum-preserving pancreatic head resection on the endocrine pancreas function in patients with chronic head pancreatitis]. 134 82

In order to better understand the mechanisms underlying the reduction in growth hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin secretion both in vivo (into hypophysial portal blood) and in vitro (from hypothalamic fragments) 5, 9 and 30 days after induction of diabetes. Experimental diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9 days after STZ administration. Chronic insulin replacement therapy in diabetic animals partly normalized somatostatin levels as well as plasma GH and glucose levels. A good correlation was observed between in vivo and in vitro experiments. Indeed, somatostatin release from hypothalamic fragments did not change 5 days after STZ-induced diabetes and significantly increased 9 and 30 days after STZ administration. The in vitro increase in hypothalamic somatostatin secretion was observed in 10 as well as in 33 mM glucose concentration in the incubation medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing factor secretion was lowered 5 and 9 days after diabetes induction. We conclude that hypothalamic somatostatin release increases in diabetic rats. These changes may contribute to the reduction in GH secretion in these animals. However, since these changes occur after the onset of plasma GH decrease, a factor(s) other(s) than somatostatin may play a causal role in the reduction in GH secretion.
 ...
PMID:Effect of diabetes on in vivo and in vitro hypothalamic somatostatin release. 135 65

Numerical changes of insulin-, glucagon- and somatostatin-positive cells in the pancreas of WBN/Kob male rats with spontaneously occurring diabetes were examined. The rats examined were divided into three different age groups: Groups I (12 weeks old) and II (33 weeks old) were clinically prediabetic and group III (60-90 weeks old) was diabetic. Serum glucose value was in the normal range in groups I and II, while it was much higher in group III. B and A cells were markedly decreased in number in groups II and III. In group II, the ratio of B to A cells was normally preserved, though the total endocrine cell number was markedly decreased as compared with that in group I. In group III, the percentage of B cells was decreased significantly. The normal ratio in group II seemed to keep serum glucose within the normal level. In addition to the total endocrine cell reduction, an altered ratio of B and A cells was considered to cause the diabetic condition.
 ...
PMID:Endocrine cell populations in the pancreas of diabetic WBN/Kob rats. 135 88

A modified insulin suppression test was adopted to assess the diurnal variation in insulin sensitivity and insulin clearance in 14 non-insulin-dependent diabetes mellitus (NIDDM) patients and eight age-, sex- and weight-matched normal subjects. The modified insulin suppression test was combined with an infusion of regular insulin, 30 mU/min x m2; glucose, 6 mg/kg x min; and somatostatin, 500 micrograms/h, for 120 minutes followed by only a somatostatin infusion for 60 minutes. Blood samplings were performed at appropriate times to obtain data on steady-state plasma insulin (SSPI), steady-state plasma glucose (SSPG as an index of insulin sensitivity), metabolic clearance and the half disappearance time (T1/2) of insulin. Blood specimens were also obtained during SSPI for measurement of erythrocyte insulin receptor binding. Each subject took the insulin suppression test twice. One test was started at 8 am and the other at 4 pm; each test was preceded by 16 hours of fasting. The order of the insulin suppression tests in each subject was randomized and balanced. In normal subjects, the SSPG level was lower in the morning than in the afternoon (118.0 +/- 43.6 vs 150.3 +/- 34.2 mg/dL, p less than 0.05). The NIDDM patients had a higher SSPG in the morning (217.7 +/- 51.4 vs 188.3 +/- 40.6 mg/dL, p less than 0.01). There was no diurnal difference in insulin clearance or the T1/2 in either normal subjects or NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Diurnal variation of insulin sensitivity in NIDDM patients and normal subjects. 135 86

A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) has been observed in type 1 diabetic patients and was hypothetically attributed to a reduced hypothalamic somatostatin tone. We have previously reported that corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone-releasing hormone (GHRH) in normal subjects, possibly by an increased release of somatostatin. To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) + TRH (200 micrograms IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was observed in seven of 13 patients, one man and six women. In these subjects, the simultaneous administration of CRH and TRH significantly reduced the GH response to TRH, as assessed by both the maximal GH mean peak +/- SE (2.18 +/- 0.67 v 9.2 +/- 1.26 micrograms/L, P less than 0.005) and the area under the curve (AUC) +/- SE (187 +/- 32 v 567 +/- 35 micrograms.min/L, P less than .001). CRH had no effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data demonstrate that the paradoxical GH response to TRH in patients with type 1 diabetes mellitus is blocked by CRH administration. This CRH action may be due to an enhanced somatostatin release. Our data also show that exogenous CRH has no effect on TSH response to TRH, thus suggesting the existence of separate pathways in the neuroregulation of GH and TSH secretion.
 ...
PMID:Corticotropin-releasing hormone inhibition of paradoxical growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics. 135 81

Changes in glucagon, insulin and somatostatin secretion induced by electrical splanchnic nerve stimulation were examined in rats treated with streptozotocin as neonates and as adults. In order to study the direct neural effects we used the isolated perfused rat pancreas with intact left splanchnic nerve in vitro. In normal rats splanchnic nerve stimulation causes significant decreases in insulin (30-40%) and somatostatin (30-50%) secretion at both 16.7 mmol/l and 1 mmol/l glucose concentrations. In the neonatal streptozotocin-diabetic rat splanchnic nerve stimulation at 16.7 mmol/l glucose decreased insulin secretion (14%) further than in the control rats (30%), however, somatostatin secretion did not decrease to the same extent. Similar results were also observed at the low (1 mmol/l) glucose concentration. On the other hand, percent decreases of insulin and somatostatin secretion induced by splanchnic nerve stimulation in the streptozocin-diabetic rats were similar to the values observed in the normal control rats. The glucagon secretion in response to splanchnic nerve stimulation at 16.7 mmol/l glucose from pancreatic Alpha cells in both types of induced diabetes is exaggerated, and the degree of exaggeration seems to parallel the severity of the hyperglycaemia. However, the splanchnic nerve stimulation-induced glucagon secretion at 1 mmol/l glucose was impaired in the streptozotocin-diabetic rats, but not in the neonatal streptozotocin-diabetic rats. These data suggest that the sensitivity of diabetic Alpha and Delta cells to sympathetic neural activation are blunted, whereas the sensitivity of Beta cells is enhanced in the diabetic animal model.
 ...
PMID:Glucagon, insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats. A study with the isolated perfused rat pancreas in vitro. 136 17

The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model.
 ...
PMID:Hyperglycemic athymic nude mice: factors affecting in vitro insulin secretion. 136 39

The interrelationship between endocrine cells of the Langerhans islands in experimental diabetes provoked in female Wistar rats are studied. The content of the insulin in B-cells, glucagon in A-cells and somatostatin in D-cells was determined by method of indirect immunofluorescence with the use of monoclonal antibodies and antiserum. It is established that an decrease of the insulin content in B-cells is followed by an increase of glucagon in A-cells and that of somatostatin in D-cells. The increase of the glucagon content is proportional to glycemia level and to the decrease of the insulin in B-cells.
 ...
PMID:[State of the pancreatic insular apparatus in experimental diabetes mellitus with varying degrees of severity in the rat]. 136 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>