Regulation of human insulin gene expression in transgenic mice

Insulin is a polypeptide hormone of major physiological importance in the regulation of fuel homeostasis in animals (reviewed in refs 1,2). It is synthesized by the beta-cells of pancreatic islets, and circulating insulin levels are regulated by several small molecules, notably glucose, amino acids, fatty acids and certain pharmacological agents. Insulin consists of two polypeptide chains (A and B, linked by disulphide bonds) that are derived from the proteolytic cleavage of proinsulin, generating equimolar amounts of the mature insulin and a connecting peptide (C-peptide). Humans, like most vertebrates, contain one proinsulin gene, although several species, including mice and rats, have two highly homologous insulin genes. We have studied the regulation of serum insulin levels and of insulin gene expression by generating a series of transgenic mice containing the human insulin gene. We report here that the human insulin gene is expressed in a tissue-specific manner in the islets of these transgenic mice, and that serum human insulin levels are properly regulated by glucose, amino acids and tolbutamide, an oral hypoglycaemic agent.     

Altered brain cholinergic enzymes activity in the genetically obese rat

Summary Genetically obese male Zucker rats (fa/fa) and their lean littermates (Fa/-) were used in this experiment. Fourteen-week-old obese and lean littermates were sacrificed and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes were assayed in specific brain regions. The assays of these enzymes indicate that obese animals and a significantly lower ChAT activity in the cerebellum, pons, and cerebral cortex and a significant increase in ChAT activity in the thalamus and hypothalamus. Meanwhile, the cerebral cortex, cerebellum, midbrain, thalamus and hypothalamus of the obese animals showed significantly higher AChE activity than their lean littermates. It was concluded from this study that obesity may be associated with changes in the enzymes of the brain cholinergic system.This work was supported by a grant from the National Aeronautics and Space Administration (NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811), and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR 03020).     

The effects of antineoplastic agents of the respiratory activity of murine lymphocytic leukemia L1210

Résumé On a évalué des effets de plusieurs agents antinéoplastiques sur la consommation d'oxygène des lymphocytes leucémiques L1210 de la souris et on les a mis en corrélation avec l'activité antitumorale de chaque composition. Cette étude indique qu'il n'y a pas de rapport apparent entre ces deux paramètres de l'action des drogues.

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Acknowledgments: The authors wish to express their appreciation to Dr.R. M. Folk of Battelle's Columbus Laboratories for his consultation and advice and toMelanie Crossin for her technical assistance.

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Supported by Grant No. AM-HE-12084-15 from the National Institutes of Health, Bethesda, Maryland, and Grant No. 7132 from The Ohio State University General Research Support Fund.