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Biomedical subjects

W L Chick

Publications and source records attributed to W L Chick.

At least 73 records · Page 4Linked to original sources
PubMed1977

Studies of streptozotocin-induced insulitis and diabetes.

Multiple small injections of streptozotocin produce a delayed, progressive increase in plasma glucose in mice within 5-6 days after the injections, in association with pronounced insulitis and induction of type C viruses within beta cells. Multiple subdiabetogenic doses of streptozotocin in rats and multiple injections of another beta cell toxin, alloxan, in mice did not induce insulitis although hyperglycemia followed the injection of larger quantities of both agents. In mice, the prior injection of 3-O-methyl-D-glucose (3-OMG) or nicotinamide attenuated the diabetic syndrome produced by streptozotocin; however, 3-OMG was more protective. Rabbit antimouse lymphocyte serum, alone, provided partial protection but, when given together with either 3-OMG or nicotinamide, effectively prevented the streptozotocin-induced diabetic syndrome. Cessation of these preventive treatments was followed by the appearance of insulitis and diabetes. These findings suggest that multiple injections of streptozotocin induce, in susceptible hosts, the triad of direct beta cell cytotoxicity, virus induction within beta cells, and cell-mediated autoimmune reaction. These factors, acting separately or in concert, appear to induce a destructive insulitis and severe diabetes. The relative importance of each component and the factors governing host susceptibility remain to be clarified.

Animals↗
PubMed1976

Partial purification and characterization of the mRNA for rat preproinsulin.

Electrophoretically homogeneous messenger RNA for rat preproinsulin has been prepared from an islet cell tumor by the use of oligo(dT(-cellulose chromatography and sucrose density gradient centrifugation. The molecular weight of the mRNA is about 210,000, as determined by polyacrylamide gel electrophoresis in formamide, and its sedimentation coefficient is 9.3 S in sucrose gradients containing 0.2 M NaCl. These results indicate that the synthesis of preproinsulin is directed by a monocistronic mRNA 600 nucleotides in length and requires approximately 55% of the molecule's coding capacity.

Adenoma, Islet Cell↗
PubMed1976

Pancreatic beta cell replication: effects of hexose sugars.

Neonatal rat pancreatic monolayer cultures were utilized to investigate the effects of various hexose sugars on insulin release and beta cell replication. Sugars tested were D-glucose, L-glucose, 3-O-methyl-D-glucose, D-mannose and D-fructose. These agents were added at varying concentrations to a control medium containing a baseline level of 5.5 mM D-glucose. Replication was estimated by incubating cultures with [3H]thymidine and determining the frequency of beta cell labelling in aldehyde-thionin stained radioautographs. Although the addition of D-glucose to the control medium resulted in a concentration-dependent increase in both insulin release and beta cell replication, the sensitivity of these two processes to glucose differed. Insulin release was stimulated by a 2.75 mM elevation in the D-glucose concentration of the control medium, while an elevation of 11 mM D-glucose was required to increase the frequency of beta cell replication. Moreover, while insulin release was maximally stimulated by an 11 mM elevation in the concentration of D-glucose, the frequency of replication continued to rise as the concentration of D-glucose was further increased. The specificity of these responses to D-glucose was demonstrated by the inability of 11 mM L-glucose or 11 mM 3-O-methyl-D-glucose to stimulate beta cell replication. D-mannose and D-fructose were less potent insulin secretagogues than D-glucose on an equimolar basis and neither compound enhanced beta cell replication at a concentration of 11 mM. However, higher concentrations of D-mannose (16.5 and 22 mM) enhanced beta cell replication, while comparable concentrations of D-fructose did not. These results indicate that the sensitivity of insulin release and beta cell replication to D-glucose differ, and that in addition to D-glucose, D-mannose is also capable of stimulating beta cell replication.

Animals↗
PubMed1975

Pancreatic beta cell culture: preparation of purified monolayers.

Procedures were developed for preparing partially purified beta cell monolayer cultures. Neonatal rat pancreases were dissociated with a trypsin-collagenase solution. Beta cells were separated from denser acinar cells by centrifuging the initial suspension in a two layer discontinous Ficoll gradient (20, 25%). Resultant cultures, highly enriched in beta cells, were further purified by incubation with cystine-free medium. This caused necrosis of the majority of fibroblastoid cells within two days, while beta cells were considerably less affected. The resultant cultures contained an average of 72% beta cells compared to 10% in untreated control cultures. Insulin release by purified monolayers remained responsive to changes in the glucose concentration of the culture medium.

Animals↗
PubMed1974

Pancreatic beta cell replication induced by glucocorticoids in subhuman primates.

Pancreatic islets were studied by means of light microsocpy, autoradiography and electron microscopy in untreated Macaca cyclopis monkeys and after the administration of large quantities of adrenal glucocorticoids. Mild hyperglycemia and profound elevations of serum immunoreactive insulin were induced by glucocorticoid injections of 1 to 3 weeks duration, with a gradual return to pretreatment levels within 2 months after cessation of treatment. Morphologic alterations included degranulation and hyperplasia of pancreatic beta cells. These were noted in association with increased numbers of labeled islet cells after the administration of (3)H-thymidine and beta cells undergoing mitotic division, and could be correlated directly with the magnitude of serum insulin elevation. Evidence of acinar-islet or duct-islet cell transformation was absent. Beta cell regranulation and the twofold increase in extractable pancreatic insulin which followed the cessation of injections demonstrated the survival and functional integrity of the newly formed beta cells.

Animals↗
PubMed1972

Studies in the diabetic mutant mouse. VI. Evolution of glomerular lesions and associated proteinuria.

Light and electron microscopic studies were performed on renal glomeruli of diabetic mutant and age-matched normal mice and correlated with alterations in urinary excretion. The glomeruli of young (prediabetic) mutants and their normal littermates were normal and identical. With increasing age, the glomeruli of normal control mice were characterized by mesangial prominence and increased thickness and nodular densities of the peripheral basal lamina. These alterations were also observed in the diabetic mutant mice but more frequently and to a greatly exaggerated degree. The diabetic mutants were polyuric and excreted a quantity of protein identified by agarose and inmunoelectrophoresis as a serum protein. The excretion of this protein preceded the recognition of the morphologic alterations and did not increase in magnitude with the progression of glomerular changes. This report challenges the theoretic concept of genetically controlled diabetic glomerular lesions and discusses possible relationships between the glomerular alterations, the presence of proteinuria and the presence of hyperglycemia.

Age Factors↗