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)

Since the development of radioimmunoassay for insulin, the diagnosis of insulinoma has been made easily. However, it has been assumed that insulinoma is heterogenous in the histological structure as well as in clinical findings. Therefore, the present study was performed to investigate the insulin response to various stimuli and to evaluate the various insulin response tests in 19 patients with insulinoma. The fasting blood glucose was 19 to 90 mg/100 ml in insulinoma and 81 +/- 5 (mean +/- S.D.) mg/100 ml in normal controls. Plasma insulin (IRI) in insulinoma ranged from 10 to 255 microU/ml, while in the control it was 14 +/- 9 microU/ml. However, insulin/blood glucose ratio increased in insulinoma (0.2-11.2) compared with the normal control (0.18 +/- 0.11). In oral glucose tolerance tests, plasma IRI increased and reached peak levels of 48-244 microU/ml, remaining elevated in most cases. In the intravenous tolbutamide test, plasma IRI increased conspicuously to 82-1,330 microU/ml and hypoglycemic coma was provoked in 54%. Plasma IRI was elevated in the intravenous glucagon test and reached the peak levels of 85-400 microU/ml, which exceeded those of the control group. Plasma IRI increased to more than 100 microU/ml after arginine infusion and formed bizarre curves. There were no correlations between plasma IRI response to various stimuli and malignancy, type of B-granule or insulin content of insulinoma tumors. It is concluded that fasting plasma IRI, insulin/glucose ratio, tolbutamide test and glucagon test are highly valuable for the diagnosis of insulinoma.
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PMID:Plasma insulin response to various secretagogues in insulinoma. 628 49

The diazoxide infusion test (600 mg i.v. over a 1-hour period) was performed in 12 patients bearing single benign islet B-cell adenoma and in 6 normal subjects. Blood glucose, plasma insulin and glucagon concentrations were measured every 15 min during the infusion and thereafter up to 150 min. In insulinoma patients, blood glucose levels failed to increase significantly while in the control group a significant rise starting from 30 min persisted throughout the test (p less than 0.05 or less). Plasma insulin mean levels decreased significantly in normal subjects from 30 to 60 min (p less than 0.05), while they were significantly suppressed in hypoglycemic patients from 15 to 120 min (p less than 0.02). Diazoxide administration induced in the normal group a significant decrease in glucagon levels (p less than 0.02 from 30 to 150 min) whereas no such suppression occurred in patients. In our experience, insulin response to diazoxide infusion in patients with insulinoma may provide additional information for diagnosis.
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PMID:Diazoxide infusion test in patients with single benign insulinoma. 630 33

In 1966, during cholecystectomy for cholecystolithiasis, a 56-year-old man was found to have islet-cell carcinoma metastatic to the liver; his fasting serum glucose level was normal. In 1971, he developed peptic ulcer disease and symptoms of fasting hypoglycemia; inappropriate secretion of insulin was shown. His primary pancreatic tumor was removed in 1973. During the next 9 years, his liver metastases continued to grow and his fasting serum glucose level was maintained at 35 to 116 mg/dL with diazoxide and hydrochlorothiazide therapy. In 1982, he developed clinical evidence of the glucagonoma syndrome, with glucagon levels between 4000 and 11 000 pg/mL. Since then, his fasting serum glucose level has been maintained at 58 to 119 mg/dL without medication. This patient has survived 17 years with a malignant insulinoma and without islet-cell chemotherapy. His course shows that malignant insulinomas may secrete other peptide hormones that can induce various clinical syndromes.
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PMID:Metastatic insulinoma with long survival and glucagonoma syndrome. 631 34

An islet cell tumor, characterized by proinsulin level significantly elevated above normal human pancreas, has been found to contain insulin- and glucagon-degrading activity. Examination by chromatography on Sephadex G-75 of the degradation products formed from insulin showed A chain, and B chain rich-A chain aggregate as previously found with rat pancreatic islets. There was, however, little conversion of A chain to low molecular weight components indicating that insulinoma peptidase that has been found to degrade glucagon at about pH 6.8 degraded that A chain to a markedly lower rate. In contrast to the insulin-degrading activity, which was activated by glutathione in the presence of EDTA, the peptidase activity was not affected by the thiol compound. The activity of the peptidase was markedly inhibited by chelating agents, i.e., EDTA and o-phenanthroline, whereas chymotrypsin and trypsin inhibitors, i.e., TOS-PheCH2Cl, TOS-LysCH2Cl, soybean and pancreas trypsin inhibitor were found to have no effect.
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PMID:Thiol-protein disulfide oxidoreductase and peptidase activities in insulinoma tissue. 632 44

Four patients, treated with pentamidine because of Pneumocystis carinii pneumonitis, displayed severe fasting hypoglycemia during this treatment. Diabetes mellitus appeared later, requiring insulin therapy in the three of them who survived more than a few weeks. The metabolic study, performed in two cases during the hypoglycemic period, demonstrated inappropriately high insulin levels in the postabsorptive state. 28 +/- 1 microunits/ml (blood glucose 41 +/- 4 mg/dl) and 86 +/- 5 microunits/ml (blood glucose 15 +/- 5 mg/dl) vs. 15 +/- 3 microunits/ml in 10 control subjects and 55 +/- 3 microunits/ml in 6 patients with a verified B-cell tumor, respectively. Poor B-cell secretory responses followed the stimulations by oral glucose (maximal increment over basal: +5 microunits/ml vs. + 40 microunits/ml in control group and +77 microunits/ml in the insulinoma group), by i.v. arginine (maximal increment + 10 and +28 microunits/ml, respectively, vs. +55 in the controls and +90 microunits/ml in the insulinoma group) and by i.v. glucagon (+10 and +23 microunits/ml, respectively) vs. +40 microunits/ml in both the control and the insulinoma groups). Plasma cortisol and glucagon, and the A-cell response to arginine were higher than normal. These high, nonsuppressible, nonstimulable insulin levels and the sequence of hypoglycemia followed by insulin-dependent diabetes mellitus is consistent with the hypothesis of a selective toxicity turned towards the B-cells. In vitro incubation of islets with pentamidine 10(-10) M produced a passive release of insulin, followed by a significant decrease in B-cell response to glucose + theophylline. It is suggested that pentamidine can induce hypoglycemia because of an early cytolytic release of insulin, and then diabetes mellitus because of B-cell destruction and insulin deficiency.
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PMID:Diabetes mellitus following pentamidine-induced hypoglycemia in humans. 675 11

In order to clarify the mechanism of insulin secretion, responses of insulin (IRI) and C-peptide (CPR) in plasma to various stimuli were investigated in normal subjects and patients with diabetes mellitus, liver cirrhosis, chronic nephritis or insulinoma. The response of plasma IRI and CPR to oral glucose load was less marked in the mild and moderate diabetes groups than in the normal controls. Neither IRI nor CPR in the severe diabetes group responded to oral glucose. The patients with liver cirrhosis revealed an exaggerated and delayed response of IRI and CPR, and a lowered CPR/IRI ratio, indicating a remarkable response of IRI to glucose. In contrast, the patients with chronic nephritis showed a prominent rise of CPR alone. In the insulinoma patients, both plasma IRI and CPR increased after glucose load. In the response to glucose, there was approximately 30-min lag time between the peaks of IRI and CPR in the normal controls and the patients with various diseases. Following arginine infusion, plasma IRI and CPR increased in the normal subjects and the patients with moderate diabetes. In the normal subjects, plasma IRI reached a peak at 6 min and 3 min in response to tolbutamide and glucagon, respectively, which elicit an abrupt and sharp rise of insulin from B-cells. However, diabetic patients showed a minimal change in plasma IRI and CPR, whereas there was an exaggerated response of plasma IRI and CPR in insulinoma patients. In analysis of responses of plasma IRI and CPR to tolbutamide or glucagon, there was a lag time longer than 10 min in the normal subjects. The present study confirms the concurrent release of C-peptide from the B-cells in the secretion of insulin. In addition, it was suggested that insulin and C-peptide are mainly handled in the liver and the kidney, respectively. Furthermore, a longer lag time between the peaks of IRI and CPR in response to tolbutamide or glucagon did not necessarily indicate a simultaneous release of insulin and C-peptide from the B-cell, but a delayed release of the latter.
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PMID:Analysis of insulin secretion based on changes in plasma insulin and C-peptide in man. 676 99

Reactive hypoglycemia is being diagnosed with increasing frequency. We compared plasma glucose, insulin, glucagon, epinephrine, and norepinephrine responses to an oral glucose tolerance test and to a mixed meal containing equivalent carbohydrate in 33 patients who had been referred to our institution with a presumed diagnosis of reactive hypoglycemia and in 2 patients who had insulinomas. In addition, a control group of 36 normal volunteers underwent the meal study. During the meal studies, electroencephalograms were obtained. Despite provocation of hypoglycemia by the oral glucose tolerance test, no consistent relationship between hypoglycemia and symptoms was observed. Despite similar symptoms, hypoglycemia did not develop after the meal test in the 33 patients without insulinomas. Both patients with insulinoma became hypoglycemic after ingestion of the meal. When a physiologic stimulus such as a meal is used to duplicate the daily dietary experience of patients, reactive hypoglycemia in the absence of a pancreatic pathologic lesion is an uncommon occurrence.
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PMID:Oral glucose tolerance test compared with a mixed meal in the diagnosis of reactive hypoglycemia. A caveat on stimulation. 687 81

The features of 41 proven or suspected cases of pancreatic glucagonoma and one possible case of renal glucagonoma have been reviewed. Glucagonoma is one form of islet cell neoplasm and involves pancreatic alpha cells. It may occur more frequently in women and is more likely to be malignant than insulinoma. Patients may present with glucose intolerance, an erythematous, eczematous dermatitis, glossitis, stomatitis, vaginitis and unexplained weight loss. Anemia, hypoproteinemia, hypoaminoacidemia and hypolipidemia may also be present. Malignant glucagonoma metastasizes frequently to liver. An evaluation for possible glucagonoma may be considered in a patient with the characteristic eczematous dermatitis, glossitis or stomatitis and glucose intolerance, an unusual or atypical history of diabetes mellitus, or hepatomegaly with other characteristics of glucagonoma. Initial evaluation may include measurement of fasting plasma glucagon concentration, and an oral glucose tolerance test with measurements of plasma glucose and glucagon levels. Extreme fasting hyperglucagonemia, and a paradoxical rise in plasma glucagon concentrations after glucose ingestion should strongly suggest the presence of glucagonoma. Radiographic demonstration of pancreatic glucagonoma is best carried out by celiac arteriography. Surgical excision of the tumor is the treatment of choice. Nonresectable lesions may respond to chemotherapy with streptozotocin. Treatment for the various dermatologic or metabolic complications of glucagonoma which include glucose intolerance, hypoproteinemia, hypocholesterolemia and anemia may not be satisfactory. Glucose intolerance is usually mild and may be adequately treated with dietary or insulin therapy. Rarely, glucagonoma with massive destruction of the pancreas or other factors may induce severe glucose intolerance. In contrast, the anemia, skin rash, and hypoproteinemia do not respond to conservative therapies tested thus far. Glucagonoma is a model for studying the importance of glucagon in causing the hyperglycemia of diabetes mellitus. Study of patients with glucagonoma does suggest that glucagon has some role in the etiology of hyperglycemia in diabetic states; however, as in studies on diabetes, investigations on glucagonoma do not demonstrate that glucagon has a primary role in producing severe glucose intolerance.
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PMID:Clinical and metabolic aspects of glucagonoma. 698 81

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postgastrectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.
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PMID:Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis. 699 72

Three patients with the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome were studied. All had watery diarrhea, hypokalemia and hypercalcemia. Plasma vasoactive intestinal polypeptide (VIP) levels determined by radioimmunoassay were markedly elevated in these patients, indicating that they had VIP-producing tumors. Plasma VIP levels determined serially after the operation indicate that its determination is useful in estimating the effect of a treatment. As for multiple endocrine neoplasia type 1 (MEN1), two out of the three cases belonged to this category. Patient 1 had a brother with insulinoma, and in case 2, even though there was no family history, the autopsy revealed not only multiple tumors of the pancreas but also pituitary adenomas, chief cell hyperplasia of the parathyroid glands, thyroid adenomas and adrenocortical adenomas. VIP and other hormones in the tumors as well as in the plasma were examined extensively in these cases. In case 1, VIP, gastrin and calcitonin were produced in the tumor and only plasma VIP levels were elevated. In case 2, with multiple tumors, tumor 1 produced VIP, glucagon pancreatic polypeptide, gastrin and calcitonin, and tumor 2, VIP, pancreatic polypeptide, gastrin and beta-melanocyte stimulating hormone. In this case, plasma VIP, pancreatic polypeptide and glucagon levels were elevated. In case 3, VIP and calcitonin were produced in the tumor, and plasma VIP and calcitonin levels were elevated. These results indicate that (1) VIP is a good tumor marker for the WDHA syndrome due to VIP-producing tumors; (2) patients with the WDHA syndrome are sometimes associated with MEN1; and (3) VIP-producing tumors are multiple hormone-producing tumors, and VIP predominantly elevated in the plasma results in the WDHA syndrome, although other hormones such as pancreatic polypeptide, glucagon and calcitonin are sometimes found to be elevated in plasma without contributing to the clinical features.
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PMID:Clinical and hormonal aspects of the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing tumor. 701 8


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