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)

An aplastic mammary carcinoma (AMC) grew slower in hypoglycemic mice (caused by fasting or by daily insulin injections) and in hyperglycemic mice (caused by alloxan or streptozotocin, or by daily injections of glucose) than in normoglycemic mice. The tumor was able to adapt to the unfavourable conditions of the diabetes; cells, when transplanted from diabetic donors into diabetic recipients, secreted immunoreactive insulin (IRI) and immunoreactive glucagon (IRG), which are deficient in the diabetic hosts. In the terminal (hypoglycemic) phase of tumor growth, the concentrations of glucose, IRI and IRG decreased. The immunological reactivity of the host animals was reduced in the hypoglycemic terminal phase. The tumor cells taken from hosts in this phase behaved differently from the cells taken in the normoglycemic phase. The "hypoglycemic" cells grew more slowly in healthy mice; the intensity of their DNA synthesis was diminished, their response to antitumor therapy was weaker. Furthermore, it was necessary to transplant more of these cells to obtain tumors in all recipients, and they lost their ability to adapt to diabetic conditions (i.e. secreted neither IRI nor IRG). Hypoglycemia was apparently the immediate cause of death in mice with AMC. Injections of glucose or glucagon into mice with AMC eliminated the hypoglycemia temporarily and postponed the death by 4 days. Mice treated with glucagon and with chemotherapy or immunotherapy survived 6-9 days longer than mice treated with chemo- or immunotherapy alone. Some of these differences between the end-stage and the progressively growing tumors could be explained in terms of tumor cell kinetics but some could be attributed to metabolic conditions of the host caused in part by the tumor.
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PMID:Different endocrinological properties, growth rate and sensitivity to chemotherapy of aplastic mammary carcinoma in normo- and hypoglycemic phase of tumor growth. 675 72

The effects of tumor growth on lipid metabolism were investigated by evaluating serum lipids, lipoprotein lipase activity (LPLA), the lipogenic enzymes, urinary catecholamines along with serum insulin and glucagon levels. We injected 1.5 X 10(6) cells of rat mammary tumor, AC33, and killed the rats on the 18th day. Serum triglycerides and free fatty acids of the tumor-bearing (TB) rats increased 4 and 5 times, respectively, more than the control (C) rats. Total liver lipids were not significantly different between the two groups. Tumor growth produced a 70% decrease in total epididymal fat pad LPLA; there were no changes in soleus muscle LPLA. Serum insulin levels of the TB rats were 49% less than the C rats. The TB rats had significantly lighter epididymal fat pads and lower activities of adipose fatty acid synthetase and citrate cleavage enzyme. Urinary catecholamines of the TB rats were reduced over 30% compared with the C rats. These results show that the hypertriglyceridemia of the TB rats may be due, in part, to a deficiency of adipose tissue LPLA. The data also suggest that the effects of the tumor on lipid metabolism may be mediated through insulin.
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PMID:Changes in the activities of lipoprotein lipase and the lipogenic enzymes in tumor-bearing rats. 698 80

Insulin and glucagon injected separately or simultaneously into CBA, C57BL, A, or C3Hf/Bu mice with aplastic carcinoma, fibrosarcoma, melanoma B16, Ehrlich tumor, lymphatic leukemia, or thymoma suppressed tumor growth and prolonged the mouse's mean survival time. Basic mechanistic features of growth retardation by insulin and glucagon were delineated for aplastic carcinoma and fibrosarcoma. In mice bearing these 2 tumors, stimulated plaque-forming capacity and phagocytosis were shown for these hormones. Cyclophosphamide abolished the growth retardation. Insulin- and glucagon-induced tumor suppression appeared mainly mediated by maintenance of high immune reactivity and phagocytosis.
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PMID:Retarded growth of murine tumors in vivo by insulin- and glucagon-stimulated immunity and phagocytosis. 701 67

Melanoma B-16 grew slowly in mice with hyperglycemia induced by alloxan, glucagon, or glucose. The mechanism of retarded tumor growth is different and depends on the origin of hyperglycemia. The concentration of immunoreactive insulin in blood of mice with melanoma and in the tumor tissue is increased in nondiabetic as well as in diabetic mice. The chemotherapy of melanoma in diabetic mice is as effective as in nondiabetic mice whereas immunotherapy in diabetic mice is not effective. Combined chemoimmunotherapy of melanoma in diabetic mice is more effective than either therapy alone only when mice are given a daily dose of insulin.
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PMID:Growth and treatment of B 16 melanoma in hyperglycemic mice. 740 88

Streptozotocin diabetes prevents induction of pancreatic tumors in several animal models, suggesting a pivotal role for islet cell products in the pathogenesis of pancreatic cancer. To test the hypothesis that altered gastrointestinal peptide levels in streptozotocin diabetes influence tumor growth, human pancreatic cancer cells (MIA PaCa-2) were implanted subcutaneously into streptozotocin diabetic nude mice. After 3 weeks, tumors in the control group weighed 43 mg and tumors in the diabetic group weighed 12 mg (P < 0.001). Plasma insulin and IGF-1 levels were significantly decreased in the streptozotocin-treated animals compared to those of control (insulin: 23 microU/ml vs 31 microU/ml, P < 0.001; IGF-1: 254 ng/ml vs 324 ng/ml, P < 0.001). In contrast, somatostatin and glucagon were significantly elevated in the streptozotocin diabetic group relative to control levels (somatostatin: 179 pg/ml vs 54 pg/ml, P < 0.001; glucagon: 290 pg/ml vs 134 pg/ml, P < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd = 15.5 nM), IGF-1 (Kd = 30.0 nM), and somatostatin (Kd = 2.5 nM) on the MIA PaCa-2 cells. Receptors for glucagon were absent. In an in vitro cell proliferation assay, cell division was promoted by insulin (P < 0.01, max + 11%) and IGF-1 (P < 0.01, max + 10%). Somatostatin inhibited cell division (P < 0.01, max - 18%). No effect was seen with glucagon. The growth of pancreatic cancer, particularly in diabetes, may be influenced by gut peptides in a receptor-dependent fashion.
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PMID:GI hormonal changes in diabetes influence pancreatic cancer growth. 779 56

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82

The neuropeptide somatostatin (SRIF) is widely expressed in the brain and in the periphery in two main forms, SRIF-14 and SRIF-28. Similarly, the presence of SRIF receptors throughout the whole body has been reported. SRIF produces a variety of effects including modulation of hormone release (e.g. GH, glucagon, insulin), of neurotransmitter release (e.g. acetylcholine, dopamine, 5-HT), and its own release is modulated by many neurotransmitters. SRIF affects cognitive and behavioural processes, the endocrine system, the gastrointestinal tract and the cardiovascular system and also has tumor growth inhibiting effects. Initially, two classes of SRIF receptors have been proposed on the basis of biochemical and functional studies. However, the recent cloning of five putative SRIF receptor subtypes which belong to the G-protein coupled receptor superfamily suggests that SRIF mediates its various effects via a whole family of receptors. Here we review, in this new context, the molecular pharmacology of the SRIF receptor subtypes present in the brain and in the periphery, and address the question of nomenclature of SRIF receptors.
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PMID:Molecular pharmacology of somatostatin receptors. 787 Jan 82

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.
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PMID:The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth. 818 58

Surgical resection has been the standard approach for primary and metastatic liver tumors. Long-term survival, however, is limited because of recurrence or hepatic decompensation. Failure of chemotherapeutic regimens or liver transplantation (OLT) to prevent recurrence has resulted in the need for multimodality therapies. We report our experience with preoperative hepatic arterial chemoembolization (CET) followed by OLT in highly select patients. Over a 33-month period, 23 of 41 patients (56%) referred with primary (n = 16) or metastatic neuroendocrine (n = 7) liver tumors met eligibility requirements. Despite mild, self-limited chemical hepatitis, CET was well tolerated in all but three elderly patients who succumbed to liver failure. Four of five patients ultimately received OLT. Three are alive and free of disease at a mean followup of 17 months, one died of recurrent hepatocellular carcinoma, and one (NET) remains well at 33 months with elevated glucagon levels but no measurable disease. All NET patients are alive with resolution of hormonal symptoms. Four of five noncirrhotic patients died of disease, and one has progressive tumor growth. Although OLT following CET achieves superior survival, its application is limited to a minority of patients with such tumors. Careful pretreatment staging and patient selection combined with caution in the use of CET in elderly cirrhotic patients is critical to the success of such therapies.
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PMID:Intrahepatic arterial chemoembolization for hepatocellular carcinoma and metastatic neuroendocrine tumors in the era of liver transplantation. 875 63

When rats bearing the 13,762 mammary carcinoma were treated with intravenously administered creatine analogs, cyclocreatine, beta-guanidinopropionic acid or creatine phosphate on days 4 through 8 and 14 through 18 post tumor implantation, the tumor growth delay produced varied with whether the animals were drinking water or sugar water over the course of the study. The tumor growth delays increased when the animals drank sugar water from 9.3, 1.6 and 7.6 days for cyclocreatine, beta-guanidinopropionic acid and creatine phosphate, respectively, to 15.0, 6.3 and 12.6 days. Blood glucose was decreased over the course of the creatine analog treatment regimen and the skeletal muscle transport protein GLUT-4 increased 1.5 to 2-fold with the creatine analog treatments. Plasma insulin was profoundly decreased to 20-25% of normal by the creatine analog treatment while plasma glucagon levels were increased. Plasma somatostatin increased 3- to 4-fold during the administration of the creatine analogs. These results implicate alterations in pancreatic hormone balance in the antitumor activity of these creatine analogs.
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PMID:Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism. 962 6


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