Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide (SMS), a somatostatin analogue, is an established antigrowth peptide, but it does not effectively inhibit the growth of insulinoma cells. In order to study the mechanisms that underlie this apparent lack of an antiproliferative effect on insulinoma tumor cells we established the rat insulinoma cell line, RINm5F, in culture. Cells in culture were tested by incubation in media with and without SMS. To study tritiated [3H]-thymidine incorporation into extracted DNA (TTID), 2 muCi/well of 3H was added for 24 hr, and cells were harvested and assayed for TTID (cpm/microgram DNA). Insulin (IRI) and intracellular cAMP (cAMPi) were measured by RIA. To study the effects of SMS on insulin secretion, conditioned media were sampled after 24 hr. To study the effects of cAMPi, conditioned medium was used to extract cAMPi following incubation with SMS for 15 min. Increasing concentrations of SMS had no significant effect on TTID in the presence of 1% FBS. Trypan blue exclusion tests showed > 90% viable cells throughout all stages of these experiments. There were no significant differences in cell numbers and protein content in the presence of SMS. There was a significant decrease in the secretion of insulin and intracellular cAMP levels in response to 50 nM SMS. However, SMS significantly inhibited TTID in RINm5F cells following a 4-hr pretreatment with pertussis toxin (PT) (23553 +/- 1747 vs 20635 [cpm/microgram DNA] +/- 1983 [SEM], P < 0.01). We conclude that the inhibition of insulin secretion by SMS is associated with an attenuation of cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of somatostatin action in RINm5F cells in culture: preliminary evidence for possible altered G protein function. 135 94

We studied the long-term change in glycemic level in a model of non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR). Two-day-old male SHR were intraperitoneally injected with 37.5 to 75.0 mg/kg of STZ or vehicle alone as control. According to nonfasting plasma glucose levels at 12 weeks of age, rats were divided into mild (less than 16.8 mmol/L) and severe (greater than or equal to 16.8 mmol/L) diabetes groups. In the mild diabetes group (n = 5), plasma glucose decreased significantly from 14.2 +/- 1.8 mmol/L (mean +/- SEM) at 20 weeks to 7.3 +/- 0.3 mmol/L at 52 weeks (P less than .05) with progressing age. At 52 weeks, overnight fasting plasma glucose levels were significantly lower and serum immunoreactive insulin (IRI) was higher than in controls, respectively (4.1 +/- 0.3 v 5.7 +/- 0.3 mmol/L, P less than 0.01; 625 +/- 50 v 409 +/- 50 pmol/L, P less than .05), and insulinoma was found in 60% of rats. Therefore, the recovery from hyperglycemia may be attributed to the development of insulinoma. In the severe diabetes group (n = 6), plasma glucose remained high until 28 weeks (27.2 +/- 1.5 mmol/L), but thereafter decreased with age, as it did in the mild diabetes group (13.7 +/- 3.5 mmol/L at 52 weeks, P less than .005). However, no insulinoma was found, and the mechanism for the recovery was unclear. The present study demonstrates that hyperglycemia spontaneously ameliorates in a neonatal STZ diabetes model of SHR, although this phenomenon may be strain-related.
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PMID:Spontaneous recovery from non-insulin-dependent diabetes mellitus induced by neonatal streptozotocin treatment in spontaneously hypertensive rats. 182 2

Cells within rat islets of Langerhans are typically organized as a core of B-cells, surrounded by the other cell types. When mixed in culture, primary islet cells and insulinoma (RIN2A) cells form aggregates where B-cells are centrally located, surrounded by non-B-cells, while RIN-cells segregate as the outermost layer. To gain insight into the molecular basis underlying this nonrandom cellular organization, the aggregation properties of the three cell populations were studied. Isolated islet cells were separated into B-cells and non-B-cells by autofluorescence-activated cell sorting (FACS). In a short-term aggregation assay, primary B-cell aggregation in the absence of calcium was only 19 +/- 3.7%, compared to the 67 +/- 2.9% seen in the presence of calcium (mean +/- SEM; P less than 0.001; n = 7). By contrast, non-B-cell aggregation and RIN cell aggregation in the absence of calcium (62 +/- 2 and 66 +/- 2%, respectively) were only slightly less than with calcium (70 +/- 3 and 76 +/- 3%). The surface density of the Ca2(+)-independent neural CAM (NCAM) was therefore measured by flow cytometry and found to be 2.64 +/- 0.82-fold higher in non-B-cells, compared to that in B-cells (P less than 0.01; n = 3). Even higher levels were found on RIN cells. In the three cell types, NCAM-140 was the only molecular form detected by immunoblotting. In conclusion, differences in the calcium dependency of aggregation and in the levels of NCAM are demonstrated among islet B-cells, non-B-cells, and RIN cells. Because cell-cell adhesion is crucial for the maintenance of adult tissue, these aggregation specificities might contribute to the concentric segregation of islet cell types in culture and to the nonrandom distribution of cells within rat islets.
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PMID:Differences in aggregation properties and levels of the neural cell adhesion molecule (NCAM) between islet cell types. 225 82

Twelve-hour metabolic profiles have been measured in six patients with insulinoma and results compared with normal subjects of similar age and weight. Fasting blood glucose was lower (mean +/- SEM 2.9 +/- 0.3 mmol/l vs 5.0 +/- 0.2 mmol/l) and plasma insulin higher (20.0 +/- 3.9 mU/l vs 7.2 +/- 1.6 mU/l) in insulinoma patients. Over the 12-h period blood glucose, pyruvate and glycerol were significantly lower, and plasma insulin, blood lactate, alanine and plasma non-esterified fatty acids (NEFA) significantly higher in insulinoma patients. Overall the concentration of blood total ketone bodies was significantly higher in insulinoma patients. Values were higher in the early part of the day but lower later in the day and did not show the marked pre-meal rise observed in the normal subjects. The raised NEFA and ketone bodies are of particular interest as they may be a source of fuel supply in the presence of relative glucose deficiency.
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PMID:Metabolic profiles in patients with insulinoma. 255 Jan 66

In view of the ability of ketones to partially replace glucose as an alternative fuel in the brain, the potential protective effects of diet-induced ketosis were examined in male NEDH rats with hypoglycaemia due to a serially transplantable radiation-induced insulinoma. Ketosis was induced by daily oral administration of medium chain triglycerides to normal rats and to insulinoma-bearing rats 1 day after subcutaneous subscapular implantation of tumours fragments. All rats treated with medium chain triglycerides became ketotic within 72 hours, and plasma 3-hydroxybutyrate concentrations remained 5-10 fold elevated at 24 days. Untreated insulinoma-bearing rats became moderately hyperinsuliaemic and hypoglycaemic by 17 days, with the later manifestation of more marked hyperinsulineamia (21.6 +/- 0.8 ng/ml, mean +/- SEM) severe hypoglycaemia (1.5 +/- 0.1 mmol/l) and death by 24-28 (26 +/- 1) days. Induction and maintenance of hyperketonaemia did not affect the development of hyperinsulineamia, hypoglycaemia or the exaggerated fall of plasma glucose produced by an 8 hour fast in these rats. However by day 21, the severity of hypoglycaemia was greater in insulinoma-bearing rats receiving medium chain triglycerides, culminating in accelerated death by 22-25 (23 +/- 1) days and an accompanying 50% decrease in final tumour weight. These results demonstrate that induction of ketosis in the face of marked hyperinsulinaemia did not afford protection against the profound hypoglycaemia produced by a serially transplantable rat insulinoma.
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PMID:Effects of diet-induced ketosis in rats with hypoglycaemia due to a serially transplantable insulinoma. 282 27

Metabolic effects of 3 different sites of transplantation of cultured tumour cells from a radiation induced insulinoma (28 X 10(6) viable cells per rat) were examined in 15-18 weeks old male NEDH rats. Subscapular implantation consistently produced a highly vascularised encapsulated tumour associated with hyperinsulinaemia, hyperphagia and hypoglycaemia by 21 days, which progressed to fatal neuroglycopaenic coma at 37 +/- 3 days (mean +/- SEM). Implantation of tumour cells into the hepatic portal vein resulted in a multilobular hepatic tumour in two out of nine rats, with hyperinsulinaemia and fatal hypoglycaemia by 49-54 days. Irregularities of glucose homeostasis were observed in a further three rats by 62 days. Intrapancreatic implantation consistently produced a similar tumour to that observed at the subscapular site. Implantation into the pancreas produced the most rapid onset of hyperinsulinaemia, hyperphagia and hypoglycaemia, with survival for only 28 +/- 3 days. The results demonstrate an important effect of transplantation site on the function and metabolic consequences of the NEDH rat insulinoma.
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PMID:Metabolic effects of radiation induced rat insulinoma at pancreatic, hepatic and subscapular transplantation sites. 287 15

The metabolic effects and secretory properties of a radiation-induced transplantable insulinoma were examined in 16-17 week old NEDH rats. Subcutaneous subscapular implantation of tumour fragments resulted in hyperphagia, increased body weight gain, marked hyperinsulinaemia and severe hypoglycaemia, with the resulting death of the recipient by 27 days. Ultimate tumour size was 2.1 +/- 0.4 g (mean +/- SEM). At 3 days after transplantation, plasma glucose and insulin responses to intraperitoneal glucose, insulin, arginine and adrenaline were similar to control rats. At 20 days, plasma glucose concentrations of insulinoma-bearing rats remained low throughout glucose tolerance tests, and insulin responsiveness to glucose stimulation was absent. 2-Deoxy-D-glucose produced only a small rise of glucose concentrations in tumour-bearing rats. Insulin sensitivity was not appreciably impaired at 20 days despite severe hyperinsulinaemia and hypoglycaemia. The ability of adrenaline and propranolol to suppress plasma insulin and raise plasma glucose concentrations was also retained. At 20 days, glucagon evoked a marked plasma insulin response with no change in plasma glucose concentrations. In contrast, arginine and glibenclamide failed to stimulate insulin above high basal concentrations.
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PMID:Metabolic effects and secretory properties of a radiation-induced transplantable rat insulinoma. 288 53

The growth and metabolic effects of a transplantable radiation-induced rat insulinoma were examined in intact male and female New England Deaconess Hospital (NEDH) rats, and in parathyroidectomised or adrenalectomised male NEDH rats. Subscapular transplantation of insulinoma fragments in intact male rats consistently produced a highly vascularised encapsulated tumour associated with hyperphagia, hyperinsulinaemia and hypoglycaemia which progressed to fatal neuroglycopaenic coma by 30 +/- 0.8 days (mean +/- SEM) and 19 +/- 0.5 days for slow-growing and fast-growing tumour sublines respectively (P less than 0.001). In intact female rats transplanted with the slow-growing subline, the onset of hyperphagia was advanced by 4 days and the severity of hyperinsulinaemia and hypoglycaemia increased (21% and 36%; P less than 0.01 and P less than 0.001, respectively), resulting in a 10% decrease of survival time (P less than 0.05) and a 65% reduction of tumour weight (P less than 0.01). Transplantation of the fast-growing subline into parathyroidectomised male rats, which exhibited a 15-24% (P less than 0.05 - less than 0.01) decrease of plasma calcium, did not modify either the growth or metabolic effects of the tumour. In contrast, transplantation of this subline into adrenalectomised male rats decreased survival time by 32% (P less than 0.001) and reduced final tumour weight by 88% (P less than 0.02) without markedly affecting the onset or magnitude of the hyperinsulinaemia. These results indicate that the growth and metabolic effects of the transplantable NEDH rat insulinoma are modified by the presence of ovarian hormones and by adrenal hormones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal modification of the growth and metabolic effects of a transplantable rat insulinoma. 302 Aug 53

An important role for calcium in the cellular events leading to insulin secretion is supported by many studies. However, simultaneous measurements of changes in intracellular free Ca2+ concentrations [( Ca2+]i) and insulin release in response to secretagogues have not been performed. Using cells isolated from a glucose-responsive insulinoma, changes in [Ca2+]i were measured with the fluorescent calcium probe quin2. With the nutrient secretagogues glucose (30 mM) and D,L-glyceraldehyde (GA; 20 mM), [Ca2+]i increased slowly, reaching a peak approximately 15 min after addition of the stimulus, while KCl (25 mM) and carbachol (2 mM) led to a rapid but transient increase in [Ca2+]i. Glucose increased [Ca2+]i from 104 +/- 6 (mean +/- SEM) to 248 +/- 31 mM (n = 13), and GA caused a rise in [Ca2+]i from 96 +/- 6 to 280 +/- 39 nM (n = 4). KCl and carbachol caused a rise from 107 +/- 6 to 184 +/- 5 nM and from 98 +/- 5 to 157 +/- 5 nM, respectively (n = 5 each). When insulin release was measured simultaneously with changes in [Ca2+]i and compared to unstimulated cells, the following results were obtained. During the first 5 min of stimulation, high glucose caused a 90 +/- 12% increase in insulin release and a 72 +/- 11% rise in [Ca2+]i (n = 5). GA evoked a 122 +/- 30% increase in insulin secretion, with a 82 +/- 17% rise in [Ca2+]i (n = 3). Both KCl and carbachol caused a 58 +/- 9% increase in insulin release, with 7 +/- 4% and 50 +/- 2% rises in [Ca2+]i, respectively (n = 4 each). Insulin release was also measured in a perifusion system. It was shown that glucose (30 mM), GA (20 mM), and alpha-ketoisocaproate (30 mM) caused a biphasic release of insulin, while KCl (25 mM) and carbachol (2 mM) caused a monophasic release. The results show that [Ca2+]i increases during the stimulation of insulin secretion when measured simultaneously on the same beta-cells. However, while these changes coincide, a simple direct quantitative relationship between insulin release and the rise in [Ca2+]i could not be demonstrated.
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PMID:Glucose induces insulin release and a rise in cytosolic calcium concentration in a transplantable rat insulinoma. 302 13

The regulation of insulin secretion in patients with insulinoma is known to be abnormal. For example, physiological and pharmacological stimuli often fail to stimulate insulin in such patients. Recently, insulin has been found to inhibit its own secretion in normal subjects. To determine if insulin has this effect in patients with insulinoma, we infused insulin at rates of 1 and 10 mU/kg X min in such a patient and in eight normal subjects. Euglycemia was maintained by the euglycemic glucose clamp technique, and endogenous insulin secretion was estimated by measuring plasma C-peptide levels. In the normal subjects, plasma C-peptide declined from 1.60 +/- 0.22 (+/- SEM) to 1.16 +/- 0.17 and 0.82 +/- 0.11 ng/ml during the low and high dose insulin infusions, respectively, indicating 27% (P less than 0.01) and 48% (P less than 0.001) decreases in endogenous insulin secretion at moderately elevated and extremely elevated insulin levels, respectively. In the insulinoma patient, plasma C-peptide was 2.6 ng/ml basally, did not change during the low dose insulin infusion, and rose to 3.4 ng/ml during the high dose insulin infusion. We conclude that the feedback regulation of insulin secretion by insulin that occurs in normal subjects is absent in insulinoma patients. This finding could have pathophysiological and possibly diagnostic significance.
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PMID:Lack of suppression of insulin secretion by hyperinsulinemia in a patient with an insulinoma. 302 22


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