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Previous studies The investigation of diabetes propensity in spiny mice, performed in Geneva and Jerusalem colonies, is reviewed. Spiny mice live in semi-desert regions of the eastern Mediterranean countries. Those transferred to Geneva in the 1950s were maintained on a rodent diet supplemented by fat-rich seeds. They became obese, exhibited pancreatic islet hyperplasia and hypertrophy. Low insulin secretion response was characteristic of this species, despite ample pancreatic content of insulin. After a few months, diabetes with ketosis occurred, often suddenly, in association with islet cell disintegration. In Jerusalem the spiny mice were collected from their native habitat and placed on diets containing 50% sucrose or fat-rich seed diets. On a sucrose-rich diet, spiny mice developed hepatomegaly, lipogenic enzyme hyperactivity, and elevation in very low density lipoproteins as a result of metabolism of the fructose component mainly in the liver. No overt diabetes or pancreatic islet disintegration were observed, although insulin content and beta-cell hypertrophy and hyperplasia were apparent. On a fat-rich diet, spiny mice exhibited marked weight gain, adipose tissue growth and low hepatic lipogenesis. The obesity was accompanied by mild hyperglycemia and hyperinsulinemia with glucose intolerance leading to an occasional glucosuria after several months on the diet.

Novel experiments The sucrose diet induced an extrathyroidal elevation of triiodothyronine (T-3). Serum T-3 level and hepatic T-4-T-3 conversion were increased, while serum T-4 levels tended to decrease. The activity of the T-3-inducible hepatic mitochondrial FAD-glycerophosphate oxidase and K+/Na+-ATPase, as well as body temperature were increased, indicating that the sucrose diet was associated with enhanced thermogenesis and energy-wasting metabolic cycling. The sucrose-rich diet might exert an adaptive thermogenesis-mediated defense mechanism, protecting against excessive weight gain and disruptive pancreatic islet lesion. After 18 months maintenance on sucrose-rich versus fat-rich diets the number of animals surviving was significantly higher on the sucrose diet whereas on the fat diet a significant number of animals succumbed to expansive islet cell disruption and diabetes. Copyright (C) 2000 John Wiley & Sons, Ltd.