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)

Urachal adenocarcinoma, normal urachus, and urinary bladder were studied by histochemical methods and electron microscopy. Many argyrophil cells were found in urachal adenocarcinoma and urachal epithelium. Autofluorescence and immunoperoxidase examinations showed that the argyrophil cells possessed serotonin, glucagon, and secretin. Some of the carcinoma cells and urachal epithelial cells contained fairly large amount of mucosubstances. On the other hand, only a few argyrophil cells and very weakly PAS positive cells were observed in the urinary bladder mucosa. This study showed that there were close similarities in the histochemical and electron microscopical features between the urachal carcinoma and urachal epithelium, and suggested that the undifferentiated stem cells were able to differentiate to both glandular and endocrine cells.
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PMID:Argyrophil cells in the urachal epithelium and urachal adenocarcinoma. 639 Oct 81

A 59-year-old Japanese farmer with asymptomatic fasting hypoglycemia and with exaggerated hypoglycemic episodes induced by insulin and oral hypoglycemic agent administered for his postprandial hyperglycemia was diagnosed as glycogen storage disease type I. This diagnosis was suggested by unresponsiveness of blood glucose level to glucagon and confirmed by 13% normal level of glucose 6-phosphatase activity in liver biopsy specimen and by the presence of PAS positive amylase digestable glycogen in liver specimen. This case was associated with an incomplete type of Fanconi syndrome characterized by hyperphosphaturic hypophosphatemia, partial aminoaciduria, mild proteinuria and hyperuricosuric normouricemia in spite of the lactic acidemia due to glycogen storage disease type I. The etiology for the absence of hypoglycemia and other typical manifestations of glycogen storage disease type I was studied. The glucose production from glycogen by lysosomal alpha 1,4-glucosidase especially at prolonged fasting and the presence of postprandial hyperglycemia by insulin deficiency are regarded as responsible for keeping this patient free from typical manifestations of glycogen storage disease type I.
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PMID:A case of glycogen storage disease type I associated with an incomplete type of Fanconi syndrome; the protective role of lysosomal alpha 1,4-glucosidase and insulin deficiency against hypoglycemia. 639 62

Brunner's gland secretion in response to infusion of secretin and glucagon was studied in the rat. Secretin was infused in doses of 15, 150 and 1500 ng/kg/h. All dose significantly increased bicarbonate and protein output and depleted Brunner's glands of PAS-positive mucin. Bicarbonate secretion was related to plasma secretin concentration, and a marked stimulatory effect of secretin was found in very low, probably physiological, plasma concentrations. Maximal bicarbonate output was obtained at a plasma concentration of secretin about 20 pmol/l. Glucagon was infused at a rate of 1.0 micrograms/kg/h and did not influence secretion rate or cell morphology. Also large doses of 5.0 and 50.0 micrograms/kg/h had no effect on Brunner's gland secretion. It is concluded that secretin in very low plasma concentrations stimulates secretion of bicarbonate, protein and mucus from Brunner's glands in the rat, while glucagon has no effect, and it is suggested that secretin may be involved in the physiological regulation of Brunner's gland secretion.
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PMID:Effect of secretin and glucagon on Brunner's gland secretion in the rat. 669 42

Hepatocyte transplantation using three-dimensional (3D) matrices is under evaluation as an alternative therapy for liver diseases. It is known that hepatotropic stimulation optimizes hepatocyte engraftment. We investigated hepatotrophic stimulation by portocaval shunt operation (PCS) or pancreatic islet cotransplantation (ICT) over a period of 6 months. Lewis rats served as donors and recipients, respectively. One week prior to hepatocyte implantation PCS (group A) or a sham operation (groups B-D) was performed. Four polyvinyl-alcohol matrices, each containing 1.25 x 10(7) hepatocytes (groups A and C), 1.25 x 10(7) hepatocytes and 500 islets (group B), or cell-free culture medium (group D, control) were implanted between recipients' small-bowel mesenteric leaves. One, 3, and 6 months after implantation eight polymers from each group were harvested and analyzed by morphometry, PAS reaction, and immunohistochemistry for insulin, glucagon, and bromodesoxyuridine. Morphologically healthy-appearing hepatocytes were found in all cell transplantation groups at all times. Stimulation by either PCS or ICT significantly increased hepatocyte area at 1 and 6 months compared to unstimulated specimens (group C). Over time, an increase in hepatocyte area was noted in all groups. There were no significant differences in proliferation ratios between the three experimental groups. The initially reduced PAS reaction became normal after 3 months. 3D matrices provided a sufficient environment for transplanted hepatocytes and islets. Hepatocytes proliferated and maintained differentiation independent of hepatotrophic stimulation for at least 6 months when 3D matrices were utilized. ICT efficiently stimulated transplanted hepatocytes by means of hepatocyte area. These results justify further research on hepatocyte transplantation and ICT with regard to clinical application.
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PMID:Heterotopic hepatocyte transplantation utilizing pancreatic islet cotransplantation for hepatotrophic stimulation: morphologic and morphometric evaluation. 1037 15

Heterotopic hepatocyte transplantation (HcTx) in polymeric matrices may become an alternative to liver transplantation for metabolic disorders. Hepatotrophic stimulation by means of a portocaval shunt operation is an established, but invasive, procedure used to optimize hepatocyte engraftment in matrices. We evaluated hepatocyte and pancreatic islet cotransplantation (ICT) as an alternative noninvasive approach to hepatotrophic stimulation. Lewis rats served as donors and recipients. Hepatocytes and islets were isolated using collagenase digestion and seeded into polyvinylalcohol matrices. HcTx and ICT were compared with HcTx plus portocaval shunt and HcTx without stimulation. Matrices were investigated at 1, 3, and 6 months after implantation: the test methods applied were trichrome staining, PAS, immunohistochemistry for insulin, glucagon and incorporated BrdU, and in situ hybridization for albumin RNA. Hepatocytes expressed albumin RNA and formed conglomerates without atypias in all animals. ICT and portocaval shunting increased the number of hepatocytes and BrdU uptake. Alpha cells migrated into the islet-surrounding hepatocytes, whereas beta cells remained immobile. It is concluded that ICT and portocaval shunting supported engraftment of hepatocytes in polymeric matrices equally well. ICT did not interfere with recipient glucose metabolism and did not induce hyperproliferative premalignant foci within the transplanted hepatocytes. The technique is an attractive approach to hepatotrophic stimulation of bioartificial liver equivalents.
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PMID:Interaction of hepatocytes and pancreatic islets cotransplanted in polymeric matrices. 1059 11

The ciliated hepatic foregut cyst is an unusual solitary cystic lesion of the liver. In a series of 7 cases of hepatic ciliated cysts, we performed a histological, histochemical, and immunohistochemical study to better define the histogenesis of this rare entity. The patients were 4 women and 3 men, aged 39 to 75 years. Four patients presented with abdominal pain. In 3 cases the cyst was discovered incidentally on ultrasonography. The cysts measured from 1 to 4 cm in diameter. Microscopically, the lining of the columnar epithelium was composed of ciliated cells and mucin secreting goblet cells. The wall was composed of bands of smooth-muscle fibers surrounded by an outer fibrous capsule. The goblet cells stained with PAS, alcian blue, and high-iron diamine. The immunohistochemical study showed that endocrine cells were present within the cyst epithelium, positive for chromogranin, synaptophysin, bombesin, and calcitonin, and negative for serotonin, somatostatin, glucagon, insulin, gastrin, and pancreatic polypeptide. In all the cases, immunoreactivity of some cells for CC10 strongly suggested the presence of Clara cells. Our study shows that the epithelium lining ciliated hepatic foregut cysts has histological, histochemical, and immunohistochemical features similar to those observed in the bronchiolar epithelium. This lesion is a developmental ventral foregut abnormality that could arise from a bronchiolar bud of the tracheobronchial diverticulum.
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PMID:The ciliated hepatic foregut cyst, an unusual bronchiolar foregut malformation: a histological, histochemical, and immunohistochemical study of 7 cases. 1068 41

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller. The islets had hardly any insulin-immunoreactive cells and consisted of cells stained by anti-glucagon and somatostatin antibodies. One, three and six months after SZ-injection, a small number of cells with vacuolative changes, which were positive for PAS staining, were observed in most islets and the vacuolated cells were stained mainly by anti-insulin antibody. In addition, a number of PCNA-positive cells were observed, especially in the periphery of the vacuolated cells, while TUNEL-positive cells were not detected. This data suggests that beta-cells proliferating as a result of the replication of the resident beta-cells in islets had fallen into degeneration and necrosis by a stress, such as the glycogen deposition in hyperglycemia and hyperlipidemia. Consequently, secretion of insulin was maintained at low levels, which allowed the hamsters to live without insulin therapy in the diabetic condition for over 6 months.
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PMID:Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia. 1187 Nov 58

Rat hepatocytes were cultured on type I collagen-coated porous membranes, in Waxman's modified medium supplemented with very low concentrations of insulin (10(-9)m), glucagon (10(-10)m) and dexamethasone (10(-8)m). Under these experimental conditions, specific differentiated functions were well preserved for at least 15 days, as shown by measures of albumin secretion, EROD and PROD activities, by phase contrast microscopy and PAS and ORO staining for intracellular glycogen and lipid contents. These results suggest that this experimental system may be very useful for long-term in vitro pharmacotoxicological studies.
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PMID:Long-term culture of rat hepatocytes on porous membranes in hormonally defined serum-free medium. 2073 33

The physiological and pathophysiological regulation of glucagon secretion from pancreatic alpha cells remains a hotly debated topic. The mechanism(s) contributing to the glucose sensitivity of glucagon release and its impaired regulation in diabetes remain unclear. A paper in the current issue of Diabetologia by da Silva Xavier and colleagues (doi: 10.1007/s00125-010-2010-7 ) provides intriguing new insight into a metabolic sensing pathway mediated by the per-arnt-sim (PAS) domain kinase (PASK) that may contribute to both the paracrine and the intrinsic glucose regulation of alpha cells. Importantly, the authors show that PASK is decreased in islets from patients with type 2 diabetes, providing a potential mechanism for impaired suppression of glucagon by hyperglycaemia in this disease. Much work remains to be done to determine the exact role and mechanism of PASK in alpha and beta cells. Nevertheless, the present work introduces a new player in the metabolic regulation of glucagon secretion.
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PMID:Per-arnt-sim (PAS) domain kinase (PASK) as a regulator of glucagon secretion. 2118 96

PAS kinase (PASK) is a nutrient sensor that is highly conserved throughout evolution. PASK-deficient mice reveal a metabolic phenotype similar to that described in S6 kinase-1 S6K1-deficient mice that are protected against obesity. Hypothalamic metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR), play an important role in feeding behavior, the homeostasis of body weight, and energy balance. These sensors respond to changes in nutrient levels in the hypothalamic areas involved in feeding behavior and in neuroblastoma N2A cells, and we have recently reported that those effects are modulated by the anorexigenic peptide glucagon-like peptide-1 (GLP-1). Here, we identified PASK in both N2A cells and rat VMH and LH areas and found that its expression is regulated by glucose and GLP-1. High levels of glucose decreased Pask gene expression. Furthermore, PASK-silenced N2A cells record an impaired response by the AMPK and mTOR/S6K1 pathways to changes in glucose levels. Likewise, GLP-1 effect on the activity of AMPK, S6K1, and other intermediaries of both pathways and the regulatory role at the level of gene expression were also blocked in PASK-silenced cells. The absence of response to low glucose concentrations in PASK-silenced cells correlates with increased ATP content, low expression of mRNA coding for AMPK upstream kinase LKB1, and enhanced activation of S6K1. Our findings indicate that, at least in N2A cells, PASK is a key kinase in GLP-1 actions and exerts a coordinated response with the other metabolic sensors, suggesting that PASK might play an important role in feeding behavior.
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PMID:PAS kinase as a nutrient sensor in neuroblastoma and hypothalamic cells required for the normal expression and activity of other cellular nutrient and energy sensors. 2376 95


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