Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A case of a malignant insulinoma in a 53-year-old female is presented. In 1973, the patient underwent caudal pancreatectomy for a malignant insulinoma. Ten years later, it was discovered that the insulinoma had spread to the bones. On admission for cholecystectomy because of a gallbladder polyp and gallstones, she often experienced hypoglycemic attacks, and both calcium and glucagon provocation tests elicited marked release of insulin. Selective angiography of the common hepatic artery showed a tumor blush near the hilum of the liver. Immunohistochemical staining of the gallbladder polyp and the bone tumors proved positive for insulin. Plasma levels of insulin and prolactin were abnormally high. The patient had also been treated for a perforated duodenal ulcer and hyperthyroidism. It is concluded that this may have been a case of a multiple endocrine neoplasia.
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PMID:Malignant insulinoma with metastasis to gallbladder and bone, accompanied by past history of peptic ulcer and hyperthyroidism. 288 87

Previous studies with heterogeneous populations of pancreatic cells have provided evidence for the presence of somatostatin (SRIF) receptors in cytosol and secretion vesicles, as well as the plasma membrane. To examine the distribution of SRIF receptors between soluble and membrane fractions in a homogeneous pancreatic islet cell population, we have used the clonal RINm5F insulinoma cell line. These cells contain specific, high affinity binding sites for [125I-Try11]SRIF on the cell surface, and occupancy of these sites by SRIF and SRIF analogs correlates with inhibition of insulin secretion. Stable, steady state binding was achieved using both intact cells and membranes by performing binding incubations with [25I-Tyr11]SRIF at 22 C. Half-maximal inhibition of [125I-Tyr11]SRIF binding occurred with 0.21 +/- 0.11 nM SRIF in membranes and 0.35 +/- 0.30 nM SRIF in cells. In contrast, the binding of [125I-Tyr11]SRIF to cytosolic macromolecules was not reduced by concentrations of SRIF as high as 100 nM, demonstrating that this binding was of much lower affinity. RINm5F membranes were further purified using a Percoll gradient to prepare a microsomal fraction, which was enriched in adenylate cyclase activity, and a secretory granule fraction, which was enriched in insulin. [125I-Tyr11]SRIF binding to the microsomal fraction (3.8 +/- 0.3 fmol/mg) was 3 times higher than to secretion granules (1.2 +/- 0.2 fmol/mg). Thus, high affinity SRIF binding sites were most abundant in microsomal membranes and were low or undetectable in secretory granules and cytosol. To determine whether translocation of SRIF receptors to the plasma membrane accompanied insulin secretion, we examined the effects of various insulin secretagogues on [125I-Tyr11]SRIF binding to intact cells. Leucine (20 mM), glyceraldehyde (15 mM), forskolin (1 microM), and glucagon (1 microM) stimulated insulin release 1.5- to 4.0-fold in different experiments. However, these secretagogues did not increase [125I-Tyr11]SRIF binding. In summary, our results indicate that high affinity SRIF receptors in RINm5F cells are located primarily on the plasma membrane and that the concentration of SRIF receptors at the cell surface is independent of the secretory activity of the cells.
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PMID:Distribution of somatostatin receptors in RINm5F insulinoma cells. 289 29

The symptoms resulting from the hyperinsulinemia of severe refractory metastatic insulinoma were palliated using self-administered divided doses of a long-acting minisomatostatin analog, octreotide. The substance was well tolerated and the attributable side effects were minimal (primarily gastrointestinal complaints). There were significant improvements in peripheral edema, ascites, and serum electrolytes throughout therapy. Serum insulin and glucagon levels were largely unchanged. Computed tomography scans performed during therapy showed stabilization of pancreatic and hepatic disease. Severe, recurrent hypoglycemic episodes due to hyperinsulinemia were reduced both in number and severity for almost a three-month period. This allowed the elimination or reduction of other chronic, supportive medications and improved quality of life.
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PMID:Remission of symptoms of chemotherapy-refractory metastatic insulinoma using octreotide. 289 65

The selective binding of somatostatin-28 (SS-28) to beta cells of hamster insulinoma was characterized using HPLC-purified 125I-[Leu8,D-Trp22,Tyr25]SS-28 or 125I-SS-28. A single class of high-affinity sites (Kd = 53 +/- 5 pM) was observed with a binding capacity of 2.85 pmol/mg membrane protein. A large number of relatively low-affinity sites was found also. The order of potency of different peptides to inhibit 125I-SS-28 binding is SS-28 greater than SS-14 greater than SMS-201-995 and the respective half-maximal inhibitory doses are 0.16 nM, 10 nM and 1000 nM. CCK8 and other active pancreatic peptides (glucagon, insulin, gastric inhibitory peptide, vasoactive intestinal peptide, oxyntomodulin) do not inhibit the SS-28 receptor binding. 125I-SS-28-labeled beta membranes were successfully cross-linked using either the cleavable cross-linker dithiobis(succinimidylpropionate) (1 mM) alone or with a heterobifunctional agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB). In both cases five molecular components were revealed, after polyacrylamide gel electrophoresis of the membrane proteins and autoradiography, with the following molecular mass: 196-kDa, 132 kDa, 69 kDa, 45 kDa and 28 kDa. The labeling of 196-kDa, 132-kDa and 45-kDa species was specific in that they could be inhibited by unlabeled SS-28. The major labeled species corresponds to the 132-kDa band and no change in the mobility of this HSAB covalently bound SS-28 receptor was found after addition of dithiothreitol, suggesting that this specific receptor does not contain interchain disulphide bonds. The molecular mass of SS-28 receptors differs markedly from that of guinea-pig pancreatic acinar membranes, where a single 93-kDa protein is identified as a 125I-SS-28 receptor site in comparative experiments. Both the binding kinetics and structural differences sustain the selective action of SS-28 in the endocrine pancreas.
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PMID:Characterization of covalently cross-linked somatostatin receptors in hamster beta cell insulinoma. 289 92

RIN-m cells, cultured from a rat insulinoma, not only bind and secrete but also degrade insulin (Diabetes 1982; 31:521-31). The insulin-degrading activity resides in the cytosol and is similar to the insulin-specific proteases previously described in muscle and other tissues. It has an apparent Km of 0.15 microM for porcine insulin in crude cell-free extracts, a competitive inhibition constant for proinsulin that is close to the Km, and a lower but measurable affinity for glucagon. The enzyme is inactive at pHs below 6.0, indicating that it is not lysosomal, is completely inhibited by N-ethylmaleimide, and exhibits apparent competitive inhibition constants (microM) for the following peptides: desoctapeptide insulin, 0.043; guinea pig insulin, 0.048; proinsulin, 0.64; insulin B-chain, 1.17; glucagon, 7.0; and cyclic somatostatin, 8.6. Highly active insulin-degrading activity was found using cell suspensions of 22 cloned and 8 subcloned cell lines derived from RIN-m as well as 11 other continuous cell lines derived from a variety of nonislet tissues of rat, mouse, and human origin. Homogenates of the original rat islet tumor and cytosol of normal rat islets also contained insulin-degrading activity. Although insulin protease is present in a variety of tissues, it may have an additional regulatory function in cells that are actively synthesizing, storing, and secreting insulin.
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PMID:Cytosolic insulin-degrading activity in islet-derived tumor cell lines and in normal rat islets. 298 50

Rat insulinoma cells, which grow in culture and secrete insulin, were used to study the mechanism of stimulation of insulin release by glucagon. The parent cell line (RIN-m) and a clone that secretes high levels of insulin (5F) had been shown to possess specific receptors for glucagon. Glucagon (1 microM) stimulated a rapid increase in cyclic adenosine 3':5'-monophosphate (cAMP) that was followed by an increase in insulin secretion in both cell lines. The concentration of glucagon necessary for half-maximal stimulation of cAMP was 50 nM in parent and approximately 0.5 microM in 5F, whereas the concentration required to inhibit binding by 50% was 0.5 nM and 30 nM, respectively. In 5F, the dose-response relationships for cAMP and insulin secretion were superimposable. The glucagon effects on insulin secretion and cAMP did not require either glucose or amino acids in the incubation media. No refractoriness to glucagon stimulation of cAMP or insulin was noted. It may be concluded that there are significant differences between glucagon binding and glucagon responses in parent cells and clone 5F, there are glucagon receptors that are not coupled to adenylate cyclase, and cAMP mediates glucagon-stimulated insulin release.
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PMID:Characteristics of the interaction of the glucagon receptor, cAMP, and insulin secretion in parent cells and clone 5F of a cultured rat insulinoma. 299 Oct 48

Twelve islet cell tumors and one islet cell hyperplasia were studied with immunocytochemical and radioimmunoassay methods. With immunocytochemical staining, all six insulinomas, one mixed insulinoma-glucagonoma, and four gastrinomas were positive for insulin, insulin and glucagon, and gastrin, respectively. Pancreatic polypeptide (PP) was positive in three insulinomas and one mixed insulinoma-glucagonoma. All of the tumors were positive for neuron-specific enolase (NSE). Radioimmunoassays of tissue extracts further disclosed that all functioning tumors contained more than one pancreatic hormone. PP concentrations of two insulinomas and one mixed insulinoma-glucagonoma were higher than that of normal control pancreases. A study of protein meal-stimulated PP secretion revealed that three of the insulinoma cases and two gastrinoma cases exhibited higher plasma PP levels than the age-matched controls. The findings suggest that: both functioning and nonfunctioning islet cell tumors derive from neuroendocrine cells positive for NSE; all functioning islet cell tumors appear to contain PP in the tumor tissue as a minor component; as many as 70% of the patients with islet cell tumors present with abnormally higher plasma PP levels after protein meals; and a study of meal-stimulated PP secretion may well be used as a marker for the presence of functional islet cell tumors.
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PMID:Pancreatic polypeptide in islet cell tumors. Morphologic and functional correlations. 299 43

The difficulty of clinical and biochemical diagnosis of insulinoma lies in the extreme variability of both clinical symptoms and glycaemia/insulinaemia levels, so that neither parameter is a totally reliable diagnostic indicator. The possibility of introducing a third parameter, the non-esterified fatty acid (FFA) level, to enhance the reliability of insulinoma diagnosis was therefore investigated. The behaviour of glucose, insulin and plasmatic FFA levels and the correlation of the three parameters were studied in 4 patients whose suspected insulinomas were later surgically confirmed. The tests applied were as follows: 24 hour fast followed by endovenous glucose, oral glucose administration, tolbutamide stimulus test, adrenaline and glucagon tests. The results revealed anomalies in insulinaemia and glycaemia behaviour such as have already, in part, been described in organic hyperinsulinism, e.g. the discrepancy between insulin and glucose levels after prolonged fasting. It was also clear that the parameters examined still leave much room for uncertainly in the biochemical diagnosis of insulinomas. Numerous anomalies were also observed in the behaviour of plasmatic FFA. For example lipid mobilisation was often reduced in conditions that normally stimulate it (fasting, the administration of catecholamines). Equally the prolonged blockage of lipid mobilisation was encountered in the presence of factors that normally reduce lipolysis (endovenous glucose). On the basis of these results it is suggested that a combined assessment of glucose and plasmatic FFA levels may be a more sensitive diagnostic indicator of insulinoma than the insulin/glucose ratio commonly reported in the literature. The mechanism behind the lipid mobilisation anomalies of insulinomas is also discussed in the light of its apparent connection with the glucose/insulin interaction characteristic of the condition.
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PMID:[Biochemical diagnosis of insulinoma: correlations between blood glucose, blood insulin and the titer of plasma non-esterified fatty acids during fasting and during various diagnostic tests]. 299 70

By means of percutaneous transhepatic portal venous sampling (PTVS), plasma insulin and glucagon levels were determined simultaneously at various sites of the hepatic portal venous system in two patients with insulinoma and four patients without. In the two cases of insulinoma, an obvious rise of insulin concentration was observed at the vicinity of the tumour, while glucagon levels were not elevated in the blood samples showing an insulin peak. In the remaining four cases without evidence of insulinoma, significant step-ups of plasma insulin occurred in the splenic vein as well, but were accompanied with concomitant elevation of plasma glucagon levels in the same blood samples. Thus, by measuring insulin alone, false positive data may frequently be obtained when PTVS is performed on patients with suspected insulinomas. The simultaneous measurement of insulin and glucagon might be helpful in avoiding such errors.
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PMID:Accurate localization of insulinoma using percutaneous transhepatic portal venous sampling--usefulness of simultaneous measurement of plasma insulin and glucagon levels. 300 71


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