Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 extrahepatic diversion of essential splanchnic hepatotrophic factors may cause the liver atrophy and insufficiency that follows portacaval shunting. To investigate this, control dogs with end-to-side portacaval shunts (control-PCS, n = 6) were compared with dogs shunted 1 month after intraportal pancreatic islet autotransplantation (islet-Tx-PCS, n = 5). From the distal pancreas of each experimental dog, 1.95 +/- 0.49 X 10(5) islets were isolated by collagenase digestion and retransplanted within 3 hours. Assays of hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green), conventional biochemical liver function tests, and glucose, insulin, and glucagon responses to intravenous glucose challenge were measured monthly and when dogs were killed. Four of six control-PCS dogs were killed 32 +/- 9 days after shunting because of more than 20% body weight loss; one control-PCS dog lost only 7% of body weight by day 56 and stabilized. No significant loss of body weight occurred in islet-Tx-PCS dogs (n = 5). Liver function test abnormalities seen in control-PCS dogs were absent in islet-Tx-PCS dogs. Both control-PCS and islet-Tx-PCS indocyanine green half-life measurements were significantly (p less than 0.05) prolonged at all times, indicating equally reduced hepatic blood flow after shunting for both groups. In contrast, islet-Tx-PCS caffeine half-life periods were significantly (p less than 0.05) shorter than in control-PCS dogs and were similar to those in normal dogs, indicating a protective effect of the transplanted islets on hepatocellular function. We conclude that intraportal pancreatic islet autotransplants prevent, by the local release of hepatotrophic factors within the liver, the metabolic abnormalities and loss of hepatic function after PCS.
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PMID:Hepatic insufficiency after portacaval shunting is prevented by prior intraportal pancreatic islet autotransplantation. 250

Using a model of streptozotocin-induced, ketosis-prone, insulin-dependent diabetes mellitus (IDDM) in the cynomolgus monkey, we performed 11 intraportal transplants of collagenase-digested, Ficoll-purified pancreatic islets (9 ABO-compatible allografts and 2 concordant baboon xenografts). Islets were pretreated with ultraviolet-B irradiation and recipients received cyclosporine A immunosuppression. Two grafts never functioned, five grafts showed evidence of partial function, and four grafts (three allografts and one xenograft) showed evidence of good function, with the animals independent of exogenous insulin with morning fasting blood glucose levels less than 200 mg/dl. Because two grafts functioned only after CsA was either tapered or discontinued, we performed a related study that showed that therapeutic doses of CsA (morning trough serum level 150-250 ng/ml) impaired intravenous glucose tolerance tests (IVGTT) of normal monkeys and may contributed to graft dysfunction in our islet transplantation model. The results show that there is a decrease in release of serum insulin during an IVGTT leading to impairment of glucose utilization, while serum glucagon remains unaffected. After cessation of CsA, the IVGTT did not return to normal for 28 days. Oral glucose tolerance tests were unaffected in CsA-treated monkeys. These initial studies show that the streptozotocin-diabetic monkey is a valuable model to study IDDM and islet transplantation in nonhuman primates. We also confirm studies in rodents, dogs, and sheep by showing that CsA partially inhibits beta cell function in normal monkeys.
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PMID:Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys. 251 1

In previous studies on streptozotocin-diabetic rats, transplantation of 1,000 (but not of 400) pancreatic islets to the renal subcapsular space was followed within 10 days by near-normalization of the impaired insulin secretion and the hyperglycemia. The long-term effects were now studied by measuring insulin and glucagon secretion 3 months after transplantation of 1,000 collagenase-isolated islets in streptozotocin (70 mg/kg) diabetic rats. At this time, diabetic control rats showed marked hyperglycemia and hyperglucagonemia, whereas the basal glucose and glucagon levels had normalized in the transplanted rats. Furthermore, insulin secretion in response to glucose or arginine stimulation and glucagon secretion following arginine stimulation were normal in all transplant rats, but absent in all diabetic controls. Morphologically the transplanted islets in the renal subcapsular space appeared normal on hematoxylin-eosin staining and immunostaining with antisera directed against insulin, glucagon, somatostatin and chromogranin A/B. Thus the islet transplants normalized basal hyperglycemia and hyperglucagonemia and restored insulin and glucagon secretion on a long-term basis.
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PMID:Islet transplantation to the renal subcapsular space in streptozotocin-diabetic rats. Long-term effects on insulin and glucagon secretion. 251 96

The mechanisms that regulate collagen gene expression in hepatic cells are poorly understood. Accelerated Ca2+ fluxes are associated with inhibiting collagen synthesis selectively in human fibroblasts (Flaherty, M., and Chojkier, M. (1986) J. Biol. Chem. 261, 12060-12065). In suspension cultures of isolated hepatocytes, the Ca2+ agonist vasopressin increases cytosolic levels of free Ca2+ (Thomas, A.P., Marks, J.S., Coll, K.E., and Williamson, J. R. (1983) J. Biol. Chem. 258, 5716-5725). However, whether vasopressin's interactions with plasma membrane V1 receptors attenuate hepatic collagen production is unknown. We investigated this problem by studying vasopressin's effects on collagen synthesis and Ca2+ efflux in long-term primary cultures of differentiated and proliferation-competent adult rat hepatocytes. Twelve-day-old quiescent cultures were exposed to test substances and labeled with [5-3H]proline. Determinations of radioactivity in collagenase-sensitive and collagenase-resistant proteins were used to calculate the relative levels of collagen production. Synthetic [8-arg]vasopressin stimulated 45Ca2+ efflux within 1 min and inhibited hepatocyte collagen production within 3 h by 50%; overall rates of protein synthesis were not affected significantly. In cultures labeled with [35S]methionine, vasopressin also decreased the levels of newly synthesized and secreted albumin, but not fibrinogen, detected in specific immunoprecipitates analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Northern blot analyses using specific [32P]cDNA probes revealed 70% decreases in hybridizable levels of collagen alpha 1(I) mRNA in hepatocyte cultures treated with either vasopressin or Ca2+ ionophore A23187; hybridizable levels of albumin mRNA also fell approximately 50% following vasopressin treatment. Vasopressin did not affect collagen production in quiescent cultures of mouse Swiss 3T3, human myofibroblast or rat smooth muscle cells; and hepatocyte collagen production was unaffected by treatment with glucagon or dibutyryl cAMP. Thus, accelerated Ca2+ fluxes induced by vasopressin are associated with decreased production of hepatocyte collagen and albumin in primary cultures that simulate quiescent adult rat liver.
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PMID:Vasopressin inhibits type-I collagen and albumin gene expression in primary cultures of adult rat hepatocytes. 254 14

Three methods for the preparation of islets from human fetal pancreas (17.4 +/- 1.2 wk gestational age) were compared. In each method, the pancreases were minced and followed by 1) no collagenase digestion, 2) 5 min of collagenase digestion, or 3) 14 min of collagenase digestion. The culture conditions prevented adherence of the fragments. Culture for 6-7 wk of minced fetal pancreas without collagenase digestion resulted in fragments that were a mixture of cells positive for insulin or glucagon, ducts, necrotic debris, and other unidentified cells with complete degeneration of the acinar cells. Culture of minced pancreas digested for 5 min with collagenase resulted in fragments that superficially appeared to be islets but did not have the size characteristics of human fetal islets and contained fibrous and duct elements not seen in islets. Culture of minced pancreas digested for 14 min with collagenase resulted in islets that were released into the medium and harvested by picking. These islets were morphologically similar to islets of the intact human fetal pancreas and isolated islets from rat neonatal pancreas. These islets and fragments were viable for at least 7-8 wk in culture.
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PMID:Development of a method for isolation of islets from human fetal pancreas. 254 73

Isolation of islets of Langerhans from the pancreas by action of collagenase, a major breakthrough for physiological studies in vitro, has long appeared empirical, and the results were sometimes unpredictable. Isolation yields (number of islets obtained per pancreas) and their reproducibility, purification from exocrine remnants and vitality of the islets obtained, can improve owing to precise techniques, adapted to the architecture of collagen in the pancreas. We have tested four isolation-purification techniques in the rat pancreas. The best results were obtained by combining intra-ductal collagenase injection, with complete but moderate distension of the gland, avoiding leakage, multistep digestion (in situ and then in vitro), followed by purification on a discontinuous bovine serum albumin (BSA) gradient. Average yields were 670 +/- 40 islets per pancreas (range 570-800), versus 170 +/- 9 (range 40-350) with the technique used initially. The use of BSA discontinuous gradient improved the purification yield: 90-96% of islets obtained were concentrated in the 26/29% BSA interface. Furthermore, this technique shortened the duration of purification step: 1 hr (centrifugation gradient) vs 3 hrs (handpicked). It was verified that islets were morphologically free of exocrine tissue. Islet structure was well preserved either in conventional histology or insulin and glucagon immunoperoxidase staining. Islet vitality, as assessed by trypan blue exclusion test, was 100% of freshly isolated islets, and 89% after 24 hrs culture. Insulin secretory responses to a given stimulus were stronger than in the case of islets isolated by former techniques: 10-12 times the basal release (vs 5 times) with clear dose-response proportionality.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reproducible high yields of rat islets of Langerhans. 254 70

The release of insulin, glucagon and somatostatin from islets isolated by microdissection, and islets isolated by aid of different duration of collagenase digestion from pancreases with exocrine atrophy was assessed. Prior collagenase digestion caused an increased release of insulin and glucagon, but not somatostatin; also, the non-suppressibility of glucagon secretion despite high glucose concentration in the medium was characteristic for those islets. Additional data suggest that in the absence of intrinsic pancreatic proteases the nature of the damage conferred by collagenase to islet B- and A-cells is different. In the light of action of epinephrine, an inhibitor of insulin secretion, possible mechanisms responsible for disturbed hormone release in the presence of proteolytic enzymes are discussed.
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PMID:In vitro secretion of hormones from the islets of pancreas with acinar atrophy--influence of digestion with collagenase. 257 35

A series of experiments using isolated rat hepatocytes was carried out to establish rat liver cells in suspension as a physiological model for examining GH responses, and to determine whether acute recombinant bovine GH (rbGH) treatment of rat liver cells increased glucose output and/or suppressed fatty acid synthesis from lactate. Rat liver cells were isolated by collagenase perfusion and incubated in short-term (less than 60 min) suspension. The amount of insulin, glucagon or vasopressin required to elicit a half-maximal response was within the physiological range of the circulating hormone. When hepatocytes from normal rats were acutely (less than 60 min) treated with 0, 0.1, 10, 100 or 1000 nmol rbGH/l, rates of hepatocyte glucose output and fatty acid synthesis were unaltered. In addition, acute rbGH treatment (1000 nmol/l) did not alter hepatocyte responsiveness to insulin or vasopressin. However, acute rbGH treatment of hepatocytes isolated from hypophysectomized rats significantly (P less than 0.05) increased the rate of glucose output twofold and moderately (P less than 0.10) enhanced fatty acid synthesis. The accelerated rate of glucose production was not accompanied by an increase in the amount of glycogen phosphorylase-a. The observations with liver cells from hypophysectomized rats are not consistent with a GH receptor-transducing mechanism which is like that for glucagon (adenylate cyclase-linked) or insulin (tyrosine kinase-linked).
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PMID:Growth hormone acutely increases glucose output by hepatocytes isolated from hypophysectomized rats. 267 Dec 41

Extralobular islet of Langerhans cells were isolated from the pancreas of an infant with intractable neonatal hypoglycemia (nesidioblastosis) by digestion with a mixture of trypsin and collagenase, and subsequent purification on a gradient of fetal calf serum. These islet cells cultured in Eagle's medium containing 20% fetal calf serum formed confluent endocrine cell monolayers within 15 days. These endocrine cells were studied immunocytochemically, and their secretion products were assayed by radioimmunological methods. The large numbers of beta, alpha and delta cells present in the islets before explanation remained functional in the cultures for 30 days. The beta cells secreted large amounts of insulin throughout this period, and secretion was stimulated by raising the glucose concentration in the medium from 5.6 to 16.8 mM. Initially there was little secretion of glucagon, but this increased during the subsequent 10 days in culture. It was not inhibited when the glucose concentration was raised from 5.6 to 16.8 mM. Somastostatin secretion remained stable throughout the period of culture, but tended to rise when the glucose concentration was increased. These results show that the culture of pancreatic cells from infants with nesidioblastosis provides an interesting in vitro system for studying the biological and biochemical characteristics of endocrine cells in the human pancreas.
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PMID:Culture of islets of Langerhans from an infant with intractable neonatal hypoglycemia: cytochemical and radioimmunological studies. 269 67

Viable Hepatocytes were isolated from adult canine liver by in situ collagenase perfusion, and cultured on collagen coated borosilicate glass plates (100 X 200mm) at confluent cell density. The medium of hepatocytes in the primary culture was L-15 supplemented with aprotinin 5000U/L, proline 30mg/L, insulin 10(-8)M, dexamethasone 10(-8)M, glucagon 10(-8)M, and h-EGF 10ng/ml. Long-stroke type bioartificial liver module consisted of 200 glass plates with hepatocytes. It contained 6 billion primary cultured cells in total, that is almost equivalent to 30% of the normal canine liver. All hepatocytes in the module were quite viable during 2 weeks in the perfusion culture, and maintained various liver functions at a high level. Gluconeogenesis was 368.0 +/- 15.4mg/module/hr, albumin synthesis was 19.1 +/- 2.5mg/module/day, ureogenesis was 3.7 +/- 0.1mg/module/hr, and ammonia metabolism was 8.4mg/module/hr. Moreover, those functions were maintained at least 2 weeks in the canine plasma as well as in the culture medium with hormones. This hybrid bioartificial liver may exert various liver functions like a liver in situ.
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PMID:[Hybrid bioartificial liver using canine hepatocytes in primary culture]. 276 24


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