Summary
Primary hypersecretion of insulin has been suggested as one possibility for the genetic fault of ob/ob mice. To test this hypothesis, streptozotocin (SZO) was used to reduce permanently insulin secretion in young lean and obese mice. After establishment of hyperglycaemia and weight reduction in treated obese mice (obese-SZO), daily insulin replacement was begun in some (obese-SZO-Ins). Obese-SZO mice maintained insulin levels and body weights similar to lean controls, though they were shorter and fatter, while food intake and blood sugar levels exceeded lean values. Obese-SZO-Ins mice with reduced islet hyperplasia, but great insulin resistance, gained more weight than obese-SZO mice; had high serum insulin and controlled blood glucose; and exhibited hyperphagia. These results suggest that primary hypersecretion of insulin cannot be the genetic defect, as ob/ob mice are hyperphagic, hyperglycaemic, insulin resistant, and “obese” even when insulin levels are restricted.
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Mayer, J., Bates, M.W., Dickie, M.M.: Hereditary diabetes in genetically obese mice. Science 113, 746–747 (1951)
Bleisch, V.R., Mayer, J., Dickie, M.M.: Familial diabetes mellitus and insulin resistance associated with hyperplasia of the islands of Langerhans in mice. Amer. J. Path. 28, 369–385 (1952)
Wrenshall, G.A., Andrus, S.B., Mayer, J.: High levels of pancreatic insulin coexistent with hyperplasia and degranulation of beta-cells in mice with the hereditary obese-hyperglycemic syndrome. Endocrinology 56, 335–340 (1955)
Christophe, J., Dagenais, Y., Mayer, J.: Increased circulating insulin-like activity in obese-hyperglycemic mice. Nature (Lond.) 184, 61–62 (1959)
Stauffacher, W., Lambert, E., Vecchio, D., Renold, A.E.: Measurements of insulin activities in pancreas and serum of mice with spontaneous (“obese” and “New Zealand obese”) and induced (goldthioglucose) obesity and hyperglycemia, with consideration on the pathogenesis of the spontaneous syndrome. Diabetologia 3, 230–237 (1967)
Genuth, S.: Hyperinsulinism in mice with genetically determined obesity. Endocrinology 84, 386–391 (1969)
Abraham, R.R., Beloff-Chain, A.: Hormonal control of intermediary metabolism in obese hyperglycemic mice. I. The sensitivity and response to insulin in adipose tissue and muscle in vitro. Diabetes 20, 522–534 (1971)
Bray, G.A., York, D.A.: Genetically transmitted obesity in rodents, Physiol. Rev. 51, 598–646 (1971)
Stauffacher, W., Orci, L., Cameron, D.P., Burr, I.M., Renold, A.E.: Spontaneous hyperglycemia and/or obesity in laboratory rodents: An example of the possible usefulness of animal disease models with both genetic and environmental components. Recent Progr. Hormone Res. 27, 41–95 (1971)
Stern, J.S., Hirsch, J.: Obesity and pancreatic function. In: Handbook of Physiology, Section 7 (eds. R. O. Greep, E. B. Aspwood), pp. 644–651. Washington: American Physiological Society 1972
Fales, F. W.: Standard methods of clinical chemistry, Vol. 4 (ed. D. Seligson), p. 101. New York: Academic Press 1963
Batchelor, B.R., Stern, J.S., Johnson, P.R., Mahler, R.J.: Effects of streptozotocin on glucose metabolism, insulin response and adiposity in ob/ob mice. Metabolism 24, 77–91 (1975)
Brosky, G., Logothetopoulos, J.: Streptozotocin diabetes in the mouse and guinea pig. Diabetes 18, 606–611 (1969)
Findlay, J.A., Rookledge, K.A., Beloff-Chain, A., Lever, J.D.: A combined biochemical and histological study on the islets of Langerhans in the genetically obese hyperglycemic mouse and in the lean mouse, including observations on the effects of streptozotocin treatment. J. Endocr. 56, 571–583 (1973)
Like, A.A., Chick, W.L.: Studies in the diabetic mutant mouse: I. Light microscopy and radioautography of pancreatic islets. Diabetologia 6, 207–215 (1970)
Coleman, D.L.: Personal communication (1974)
Mahler, R.J., Szabo, O.: Restoration of insulin sensitivity in the obese mouse following suppression of pancreatic islet cell hyperplasia. Israel J. med. Sci., 8, 810–811 (1972)
Mahler, R. J., Szabo, O.: Amelioration of insulin resistance in obese mice. Amer. J. Physiol. 221, 980–983 (1971)
Stauffacher, W., Renold, A.E.: Effect of insulin in vivo on diaphragm and adipose tissue of obese mice. Amer. J. Physiol 216, 98–105 (1969)
Chlouverakis, E., Dade, F., Batt, R. A.L.: Glucose tolerance and time sequence of adiposity, hyperinsulinemia and hyperglycaemia in obese-hyperglycemic mice (ob/ob). Metabolism 19, 687–693 (1970)
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Boozer, C.N., Mayer, J. Effects of long-term restricted insulin production in obese-hyperglycemic (genotype ob/ob) mice. Diabetologia 12, 181–187 (1976). https://doi.org/10.1007/BF00428986
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DOI: https://doi.org/10.1007/BF00428986