Feeding in response to insulin and 2-deoxy-D-glucose in Zucker rats on dietary self-selection.

Abstract

SummaryAdult male fatty and lean rats of Zucker strain were given access ad libitum to either a single nutritionally complete diet, or a self selection regime with separate sources of three macronutrients, protein (casein), fat (hydrogenated coconut oil), and carbohydrate (sucrose). Animals on the single diet were fed on a powdered stock diet, and then switched to the self-selection regime. Energy intake on the self-selection regime was the same as that for the single diet condition in both fatty and lean rats. Fatty rats consumed 45% more energy than did their lean littermates. Further, fatty rats selected 47.0% of their total calories as protein, 30.1% as fat, and 22.9% as carbohydrate. The respective per centages for lean rats were 56.1, 13.0 and 30.9. In lean rats, the injection of insulin (10U/kg) or 2-deoxy-D-glucose (500mg/kg, 2DG) failed to increase energy intake, but increased carbohydrate intake 2 times by attenuating protein intake. Also in fatty rats, insulin did not increase energy intake, but it did increase carbohydrate by 50% by attenuating fat intake. 2DG decreased energy intake by attenuating carbohydrate and fat intakes in fatty rats. Fatty rats were slightly less hypoglycemic to insulin, but more hyperglycemic to 2DG than lean rats. These different self-selec tion patterns of fatty rats seemed to be associated with their endocrine, metabolic, and behavioral abnormalities.

Expression Levels of Genes Likely Involved in Glucose-sensing in the Obese Zucker Rat Brain

“…The primary hypothesis underlying this study is that mechanism of glucosesensing in pancreatic b-cells involving GK, GLUT-2 and GLP-1 provides a model for glucose-sensing in the brain. The obese Zucker rat is a good candidate for disrupted glucose-sensing because of its dysfunctional glucose regulation, hyperphagia and insensitivity to glucoprivation (Ikeda et al, 1980;Matsuo et al, 1984). The present data show notable derangements in the expression of glucose-sensing genes in all three regions measured.…”

“…Additionally, injection of GLUT-2 antisense into the lateral ventricle resulted in a decline body weight as well as food intake (Wan et al, 1998). The reduction in GLUT-2 expression in the hindbrain, observed in our study, might be related to the obese Zucker rat's hyperphagia and lack of sensitivity to the feeding effects of 2-DG induced glucoprivation (Ikeda et al, 1980;Matsuo et al, 1984).…”

“…It has been reported that regional brain glucose utilization in obese Zuckers, determined by 2-deoxy (1-3 H) glucose-6-phosphate levels, is significantly diminished compared with lean controls (Tsujii et al, 1988;Marfaing-Jallat et al, 1992). Additionally, obese Zucker rats show blunted behavioral responses to 2-deoxy-D-glucose-induced glucoprivation (Ikeda et al, 1980;Matsuo et al, 1984). It is possible that some of these abnormalities are related to disturbances of genes likely involved in central glucose-sensing mechanisms.…”

Dietary self-selection in chronically insulin-treated golden hamsters.

“…Chronic administration of long-acting insulin caused hyperphagic hamsters on a self-selection diet to derive 65% of their excess calories from fat and only 15% from protein and 20% from carbohydrate. Other species that have been studied, in contrast, show highly selective increases in carbohydrate intake in response to exogenous insulin under a variety of experimental circumstances (Andik & Denhoffer, 1949/50; Kanarek et al, 1980; Matsuo et al, 1984; Richter, 1942). During the postinsulin period, hamsters reduced their fat intake, but not their protein or carbohydrate intake, below control levels.…”

“…It has commonly been observed in species other than hamsters that insulin administration causes selective increases in carbohydrate consumption when animals have the opportunity to choose among macronutrients (Andik & Denhoffer, 1949/50; Kanarek, Marks-Kaufman, & Lipeles, 1980; Matsuo, Shimakawa, Ikeda, & Iwatsuka, 1984; Richter, 1942). This pattern of carbohydrate preference is, of course, entirely consistent both with the glucostatic theory (Mayer, 1955) and with Richter's concept of adaptive dietary choice (Richter, 1942/43), because, of the three principal dietary sources of energy (carbohydrate, fat, and protein), carbohydrate would most efficiently and rapidly counteract the insulin-induced hypoglycemia.…”