Summary
To investigate the effect of the ob gene in the heterozygous condition, plasma glucose and insulin responses of adult heterozygous lean (ob/+) mice were compared with mice of the homozygous lean (+/+) and homozygous obese (ob/ob) genotypes. The ob/+ mice consumed 24% more food than +/+ mice although body weights were similar. Plasma glucose and insulin concentrations were respectively 16% and 176% higher in ob/+ mice than +/+ mice in the freely fed state, and 44% and 88% higher during glucose tolerance tests. In 24 hour fasted ob/+ mice, plasma glucose concentrations were 23% higher than +/+ mice but plasma insulin concentrations were not significantly different. Arginine produced a greater insulin response (172%) and a greater fall in glycaemia (200%) in ob/ + mice. A significant difference in the hypoglycaemic effect of insulin in ob/+ and +/+ mice was not observed. These results demonstrate an effect of the ob gene on glucose homeostasis in heterozygous lean (ob/+) mice. The abnormalities were qualitatively similar but considerably less severe than those in ob/ob mice, suggesting that ob/+ mice might prove useful to study factors predisposing to inappropriate hyperglycaemia.
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Albano JDM, Ekins RP, Maritz G, Turner RC (1972) A sensitive precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol (Kbh) 70: 487–509
Bailey CJ, Atkins TW, Connor MJ, Manley CG, Matty AJ (1975) Diurnal variations of food consumption, plasma glucose and plasma insulin concentrations in lean and obese hyperglycaemic mice. Horm Res 6: 380–386
Bailey CJ, Flatt PR, Atkins TW (in press) Influence of genetic background and age on the expression of the obese hyperglycaemic syndrome in Aston ob/ob mice. Int J Obesity
Beloff-Chain A, Bogdanovic S, Cawthorne MA (1979) Acute regulation of insulin release by the pituitary gland in relation to hyperinsulinaemia and obesity. J Endocrinol 81: 271–279
Beloff-Chain A, Hawthorn J, Green D (1975) Influence of the pituitary gland from the homozygote (+/+) and heterozygote (ob/+) lean mouse on insulin secretion in vitro. FEBS Lett 55: 72–74
Bray GA, York DA (1979) Hypothalamic and genetic obesity in experimental animals: An autonomic and endocrine hypothesis. Physiol Rev 59: 719–809
Coleman DL, Hummel KP (1973) The influence of genetic background on the expression of the obese (ob) gene in the mouse. Diabetologia 9: 287–293
Dubuc PU (1976) The development of obesity, hyperinsulinaemia and hyperglycaemia in ob/ob mice. Metabolism 25: 1567–1574
Edwardson JA, Hough CAM (1975) The pituitary-adrenal system of the genetically obese (ob/ob) mouse. J Endocrinol 65: 99–107
Ekins RP, Newman GB, O'Riordan JLH (1968) Theoretical aspects of saturation and radioimmunoassay. In: Hales RL, Grosswitz FA, Murphy BEP (eds) Radioisotopes in medicine, in vitro studies. US Atomic Energy Commission, Oak Ridge, p 59–100
Falconer DS (1960) Selection of mice for growth on high and low planes of nutrition. Genet Res 1: 91–113
Falconer DS (1960) The genetics of litter size in mice. J Cell Comp Physiol 56 [Suppl 1]: 153–167
Flatt PR, Bailey CJ (in press) Importance of the enteroinsular axis for the insulin secretory response to glucose in obese hyperglycaemic (ob/ob) mice. Biochem Soc Trans
Flatt PR, Swanston-Flatt SK, Bailey CJ (1979) Glucagon antiserum: A tool to investigate the role of circulating glucagon in obese hyperglycaemic (ob/ob) mice. Biochem Soc Trans 7: 911–913
Flatt PR, Thornburn CC, Bailey CJ (1979) A computer approach to the analysis of radioimmunoassay data. J Endocrinol 80: 50P-51P
Grice HC (1964) Methods for obtaining blood and for intravenous injections in laboratory animals. Lab Animal Care 14: 483–493
Harris H (1966) Human biochemical genetics. Cambridge University Press, London New York, p 1–310
Herberg L, Coleman DL (1977) Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26: 59–99
Herberg L, Kley HK (1975) Adrenal function and the effect of a high-fat diet on C57BL/6J and C57B0L/6J-ob/ob mice. Horm Metab Res 7: 410–415
Hum BAL, Landon J (1971) Antisera for radioimmunoassay. In: Kirkham KE, Hunter WM (eds) Methods in radioimmunoassay. Churchill Livingstone, Edinburgh London, p 121–142
Ingalls AM, Dickie MM, Snell GD (1950) Obesity, a new mutation in the house mouse. J Hered 41: 317–318
Joosten HFP, van der Kroon PHW (1974) Enlargement of epididymal adipocytes in relation to hyperinsulinaemia in obese hyperglycaemic mice (ob/ob). Metabolism 23: 59–66
Kaplan ML, Leveille GA (1974) Core temperature, O2 consumption and early detection of ob/ob genotype in mice. Am J Physiol 227: 912–915
Polak JM, Pearse AGE, Grimelius L, Marks V (1975) Gastrointestinal apudosis in obese hyperglycaemic mice. Virchows Arch [Pathol Anat] 19: 135–150
Rodbard D (1974) Statistical quality control and routine data processing for radioimmunoassays and immunoradiometric assays. Clin Chem 20: 1255–1270
Stevens JF (1971) Determination of glucose by automatic analyser. Clin Chem 32: 199–201
Yen TTT, Lowry L, Steinmetz J (1968) Obese locus in Mus musculus: A gene dosage effect. Biochem Biophys Res Commun 33: 883–887
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Flatt, P.R., Bailey, C.J. Abnormal plasma glucose and insulin responses in heterozygous lean (ob/+) mice. Diabetologia 20, 573–577 (1981). https://doi.org/10.1007/BF00252768
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DOI: https://doi.org/10.1007/BF00252768