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)

This research investigates the use of an insulinotropic factor, glucagon-like peptide-1 (GLP-1), to enhance insulin secretion from islets within a macrocapsule. A zinc-crystallized form of GLP-1 was added to the macrocapsule device to have a longer and more controlled release of the bioactive monomer GLP-1. The type of macrocapsule device used for this study consisted of a hollow fiber (MWCO 100,000 and 1 mm inner diameter) containing rat islets and GLP-1 crystals within a poly(N-isopropylacrylamide-co-acrylic acid) (2 mol% acrylic acid) matrix. When incubating the system in media with a high glucose concentration (300 mg/dL), insulin secretion was enhanced with a >85% increase after an induction period. When the same type of system was used in a dynamic perfusion experiment, similar results were obtained. GLP-1 crystals can be an effective form to be entrapped in a bioartificial pancreas to enhance insulin secretion function, especially at high glucose concentrations.
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PMID:The effect of zinc-crystallized glucagon-like peptide-1 on insulin secretion of macroencapsulated pancreatic islets. 1122 22

Hyperzincuria is a common feature in diabetic patients, which is still not understood. Based on the above consideration, the aim of the present study was to investigate the renal handling of zinc in insulin-dependent diabetes mellitus (IDDM) patients. The glomerular filtration rate, urinary zinc excretion, zinc clearance, zinc clearance/creatinine clearance ratio, zinc tubular reabsorption, glycosuria, plasma glucose, C-peptide, glucagon, and cortisol were investigated in 10 normal individuals (Group C1 and Group C2, respectively) and 10 IDDM patients (Group E1: hyperglycemic and glycosuric and Group E2: normoglycemic and aglycosuric) during placebo or venous zinc tolerance test. The results showed that urinary zinc excretion and renal zinc clearance were increased after zinc injection in normal individuals (Group C2) and IDDM patients (Groups E1 and E2) when compared with normal individuals-placebo (Group C1). However, these renal parameters were statistically more significant in the hyperglycemic and glycosuric diabetics (Group E1). Because patients in Group E1 had the lowest plasma C-peptide levels and showed a strong negative correlation between CZn++/Ccr ratio and this hormone, we suggest that in this setting insulin inhibits urinary zinc excretion.
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PMID:Renal handling of zinc in insulin-dependent diabetes mellitus patients. 1136 78

Glucagonoma syndrome is a paraneoplastic phenomenon characterized by an islet alpha-cell pancreatic tumor, necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, stomatitis, thromboembolism, and gastrointestinal and neuropsychiatric disturbances. These clinical findings in association with hyperglucagonemia and demonstrable pancreatic tumor establish the diagnosis. Glucagon itself is responsible for most of the observed signs and symptoms, and its induction of hypoaminoacidemia is thought to lead to necrolytic migratory erythema. Liver disease and fatty acid and zinc deficiency states may also contribute to the pathogenesis of the eruption in some cases. Most patients are diagnosed too late in the clinical course for cure, but successful palliation of symptomatology can usually be achieved with surgical and medical intervention. This paper reviews the glucagonoma syndrome, paying particular attention to its cutaneous features, and provides new perspectives in our current understanding of this phenomenon.
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PMID:The glucagonoma syndrome: a review of its features and discussion of new perspectives. 1137 Jul 94

To address the solution for some of the obstacles, such as low insulin secretion, limited lifespan and aggregation of transplanted islets, encountered in developing a biohybrid artificial pancreas (BAP), polymeric materials including a reversible polymeric extracellular matrix (ECM), crystallized glucagon-like peptide-1, and oxygen carrying polymers, were prepared and their potential utilities in designing a compact and rechargeable BAP were investigated. For a synthetic, reversible ECM, high molecular weight N-isopropylacrylamide copolymer with a small amount of acrylic acid (2 mole%) was synthesized by conventional radical polymerization in benzene, and its aqueous solution above a critical polymer concentration displayed a sol-gel transition temperature near physiological temperature (33-35 degrees C) without noticeable hysteresis. The physicochemical properties of the gel with islet compatibility proved that the synthetic ECM is an appropriate matrix which can make a BAP rechargeable. Glucagon-like peptide-1 (GLP-1, 7-37) is known to have a strong stimulatory effect on insulin secretion, particularly at high glucose concentrations. When zinc-crystallized GLP-1 was entrapped along with islets in a hollow fiber macrocapsule device, insulin secretion was enhanced at a high glucose concentration (300 mg/dl) with a >85% increase in insulin secretion after an induction period. The cross-linked hemoglobin with difunctional PEO (Hb-C) was prepared to increase the high molecular weight of Hb. This prevents diffusional loss when enclosed in an immunoprotecting membrane. The Hb-C, entrapped in microcapsules, enhanced insulin secretion and improved the viability of microencapsulated islets by promoting oxygen supply to islets. The introduction of the synthetic ECM, crystallized GLP-1, and Hb-C into a BAP may provide a basis for designing a compact and rechargeable BAP (macrocapsule).
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PMID:Bioactive polymers for biohybrid artificial pancreas. 1182 19

The rheological properties of plasma and blood cells are markedly influenced by the surrounding milieu: physicochemical factors, metabolism and hormones. Acid/base status, osmolality, lipid status and plasma protein pattern are well known to exert a major influence. The oxidative stress induced by increased free radicals production decreases red cell deformability. Among circulating substances, the divalent cations magnesium and zinc improve red cell deformability probably via calcium antagonistic effects. Some metabolites like lactate or ketone bodies decrease red cell deformability, although the former has apparently the opposite effect in highly trained individuals. Endothelium-derived factors such as nitric oxide (NO) and several arachidonic acid derivatives modulate both RBC and white cell mechanics. Endothelium regulates also blood rheology via the release of PAI-1 which governs plasma fibrinogen levels. However, endothelium is not the only organ involved in the regulation of blood rheology: the kidney (by releasing erythropoietin which is a major "viscoregulatory" factor), the endocrine pancreas (via the action of insulin and glucagon on red cells), the adrenal gland (norepinephrine) and the endocrine heart (atrial natriuretic peptide) are also likely to exert important effects. Recently, increasing evidence is accumulating for a role of two other endocrine tissues in the regulation of blood rheology: the adipose tissue (free fatty acids, PAI-1, IL-6, leptin) and the pituitary gland (growth hormone-somatomedin axis, including the somatomedin carrier protein IGFBP1). These organs provide a link between body composition and hemorheology, since GH and somatomedins are major regulators of the body content in fat and water while the endocrine activity of fat mass is apparently proportional to its size. These mechanisms explain to some extent why many situations, either physiological (diet, exercise) or pathological (diabetes, uremia) are associated with marked changes in blood rheology that may in turn modify micro and macrocirculatory hemodynamics and the distribution of O(2) and fuels to tissues.
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PMID:Hormones, metabolism and body composition as major determinants of blood rheology: potential pathophysiological meaning. 1208 54

Islets of Langerhans account for 2 g of endocrine tissue in the pancreas, comprising approximately one million islets, with each containing 1000 endocrine cells. The major hormone secreted from the islets is insulin, which regulates blood glucose, the main fuel of the body. Islets also secrete glucagon, somatostatin and pancreatic polypeptide and all are involved in the paracrine mechanism. Islet cells can be stained immunohistochemically for the general endocrine markers, chromogranin A, synaptophysin, neuron-specific enolase and Leu7. Beta islet cells are well equipped with glucose transporter 2, which binds to glucose and regulates diffusion of glucose through the beta cell membrane. As all four islet hormones are initially synthesized as prohormones, all islet cells are equipped with prohormone convertase 1/3 and 2. In addition, islet cells also contain zinc-containing matrix metalloproteinases and their inhibitors, metallothionein, cyclin-dependent kinases and insulin-like growth factors, and many more hormones, peptides and enzymes. Thus, islets not only secrete insulin and other pancreatic hormones but are a complex organ whose major function is glucose homeostasis.
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PMID:New markers for pancreatic islets and islet cell tumors. 1216 99

Homeostasis of blood glucose is maintained by hormone secretion from the pancreatic islets of Langerhans. Glucose stimulates insulin secretion from beta-cells but suppresses the release of glucagon, a hormone that raises blood glucose, from alpha-cells. The mechanism by which nutrients stimulate insulin secretion has been studied extensively: ATP has been identified as the main messenger and the ATP-sensitive potassium channel as an essential transducer in this process. By contrast, much less is known about the mechanisms by which nutrients modulate glucagon secretion. Here we use conventional pancreas perfusion and a transcriptional targeting strategy to analyse cell-type-specific signal transduction and the relationship between islet alpha- and beta-cells. We find that pyruvate, a glycolytic intermediate and principal substrate of mitochondria, stimulates glucagon secretion. Our analyses indicate that, although alpha-cells, like beta-cells, possess the inherent capacity to respond to nutrients, secretion from alpha-cells is normally suppressed by the simultaneous activation of beta-cells. Zinc released from beta-cells may be implicated in this suppression. Our results define the fundamental mechanisms of differential responses to identical stimuli between cells in a microorgan.
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PMID:Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. 1264 Apr 62

1. The activities of enzymes of the urea cycle [carbamoyl phosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinase (these last two comprising the arginine-synthetase system) and arginase] have been measured in control, alloxan-diabetic and glucagon-treated rats. In addition, measurements were made on alloxan-diabetic rats treated with protamine-zinc-insulin. 2. Treatment of rats with glucagon for 3 days results in a marked increase in the activities of three enzymes of the urea cycle (carbamoyl phosphate synthetase, argininosuccinate synthetase and argininosuccinase). The pattern of change in the alloxan-diabetic group is very similar to that of the glucagon-treated group, although the magnitude of the change was much greater. 3. Comparison was made of the actual and potential rate of urea synthesis in normal and diabetic rats. In both groups the potential rate of urea production, as measured by the activity of the rate-limiting enzyme, argininosuccinate synthetase, slightly exceeds the actual rate of synthesis by liver slices in the presence of substrates. The relative activities of the actual and potential rates were similar in the two groups of animals, this ratio being 1:0.70. 4. In the alloxan-diabetic rats treated with protamine-zinc-insulin for 2.5 or 4 days there was a marked increase in liver weight. This was associated with a rise in the total hepatic activity of the urea-cycle enzymes located in the soluble fraction of the cell (the arginine-synthetase system and arginase) after 2.5 days of treatment. After 4 days of treatment the concentration of these enzymes/g. of liver decreased, and the total hepatic content then reverted to the untreated alloxan-diabetic value. 5. No effects of glucagon or of insulin in vitro could be found on the rate of urea production by liver slices. 6. The present results are discussed in relation to how far this pattern of change is typical of conditions resulting in a high urea output, and comparison has been made with other values in the literature.
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PMID:INFLUENCE OF PANCREATIC HORMONES ON ENZYMES CONCERNED WITH UREA SYNTHESIS IN RAT LIVER. 1434 1

The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. It is typically characterized on skin biopsies by necrolysis of the upper epidermis with vacuolated keratinocytes. In persistent hyperglucagonemia, excessive stimulation of basic metabolic pathways results in diabetes mellitus at the expense of tissue glycogen stores, and muscle and fat mass. Multiple (essential) nutrient and vitamin B deficiencies develop, which contribute to the dermatosis. In addition, glucagonomas may produce various other products, like pancreatic polypeptide, that add to the catabolic effects of glucagon.
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PMID:The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. 1553 29

Glucagon, secreted from islet alpha-cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of beta-cell secretory products zinc and insulin on isolated rat alpha-cells, intact islets, and perfused pancreata. Islet glucagon secretion was markedly zinc sensitive (IC(50) = 2.7 micromol/l) more than insulin release (IC(50) = 10.7 micromol/l). Glucose, the mitochondrial substrate pyruvate, and the ATP-sensitive K(+) channel (K(ATP) channel) inhibitor tolbutamide stimulated isolated alpha-cell electrical activity and glucagon secretion. Zinc opened K(ATP) channels and inhibited both electrical activity and pyruvate (but not arginine)-stimulated glucagon secretion in alpha-cells. Insulin transiently increased K(ATP) channel activity, inhibited electrical activity and glucagon secretion in alpha-cells, and inhibited pancreatic glucagon output. Insulin receptor and K(ATP) channel subunit transcripts were more abundant in alpha- than beta-cells. Transcript for the glucagon-like peptide 1 (GLP-1) receptor was not detected in alpha-cells nor did GLP-1 stimulate alpha-cell glucagon release. beta-Cell secretory products zinc and insulin therefore inhibit glucagon secretion most probably by direct activation of K(ATP) channels, thereby masking an alpha-cell metabolism secretion coupling pathway similar to beta-cells.
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PMID:Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release. 1591 3


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