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The satiating potency of cholecystokinin is an inverse function of the intensity of sweet taste
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obesity and diabetes. Using the obese Zucker rat as an experimental model of obesity, immunoreactive GIP (IR-GIP) release and release of insulin in response to glucose and GIP were studied in vivo and in vitro. Methods. Oral and IV glucose tolerance tests (OGTT, IVGTT) were performed on conscious fatty Zucker rats and lean litter mates with serum samples collected for glucose, IR-insulin (IRI) and IR-GIP determinations. The sensitivity of the isolated perfused pancreas of the same animals to glucose and GIP was assessed. Results. The glucose response to OGTT in fatty rats was indistinguishable from lean animals whereas the insulin response was 5x greater. IVGTT yielded the same pattern. The peak IR-GIP response to OGTT in 4 obese animals was 5000 pg/ml (~) compared to a ~ of 3000 in lean litter mates. The insulin response of the isolated perfused pancreas of obese rats to glucose was 3x greater than the response of lean animals, whereas the maximum in vitro response to 1 ng/ml GIP in fat animals was 18,000 vs. 7000 ~U/min from lean animals. Conclusions. Obese Zucker rats are normoglycemic, hyperinsulinemic and hyperGIPemic. An exaggerated insulin response to both OGTT and IVGTT indicates heightened B cell sensitivity. This is confirmed by in vitro perfusion studies in which glucose and GIP yielded a greatly magnified insulin response in obese vs. lean Zucker rats.
THE SATIATING POTENCY OF CHOLECYSTOKININ IS AN INVERSE FUNCTION OF THE INTENSITY OF SWEET TASTE. G.P. Smith and J. Bernz. E.W. Bourne Laboratory, N.Y. Hospital-Cornell Medical Center, White Plains, NY 10605, USA. To investigate the interaction between the positive effect of sweet taste and the inhibitory effect of cholecystokinin (CCK-8) on sham feeding, we prepared rats with chronic gastric fistulas. When the fistulas were opened after 18 h of food deprivation, rats (n=7) sham fed sucrose solutions almost continuously for 30 min. The intake of sucrose solution was a function of the percent concentration (w/v) of sucrose (Table i). Percent Sucrose Intake (mean mI±SE)
1.25 22±8.6
Table 1 2.5 5.0 35±6.3 40±5.0
i0.0 51±4.4
20.0 59±4.6
40.0 52±4.5
The inhibitory effect of CCK-8 (0.5, i, 2 and 4 ~g-kg -I) administered intraperitoneally just before presentation of 2.5, 5.0 or 10.0% sucrose solution was measured in 6 rats. The major result was that the inhibitory potency of CCK-8 (expressed as % inhibition of volume of intake) was an inverse function of the concentration of sucrose. For example, 2 ~g-kg -I CC~-8 inhibited the intake of 10% sucrose by 15%, inhibited the intake of 5% sucrose by 35%, and inhibited the intake of 2.5% sucrose by 54%. Since sham feeding eliminates the postingestive effects of sucrose, these results demonstrate that the satiating effect of CCK-8 is an inverse function of the intensity of sweet taste produced by sucrose.
CHRONIC BOMBESIN INJECTION CAN LEAD TO A PERSISTENT DECREASE OF FOOD INTAKE AND LOSS OF BODY WEIGHT IN RATS. David B. West, Robert H. Williams, Daren J. Braget and Stephen C. Woods. University of Washington, Seattle, WA. USA Although many gut hormones reduce the size of individual meals, few studies have administered these hormones over an extended period of time in an attempt to reduce body weight. Eight female Wistar rats were habituated to a schedule of food deprivation except for three ~0-minute sessions during the dark phase of the day/night cycle. Just prior to each session, the rats were given subcutaneous (sc) injections of saline followed by free access to
obesity and diabetes. Using the obese Zucker rat as an experimental model of obesity, immunoreactive GIP (IR-GIP) release and release of insulin in response to glucose and GIP were studied in vivo and in vitro. Methods. Oral and IV glucose tolerance tests (OGTT, IVGTT) were performed on conscious fatty Zucker rats and lean litter mates with serum samples collected for glucose, IR-insulin (IRI) and IR-GIP determinations. The sensitivity of the isolated perfused pancreas of the same animals to glucose and GIP was assessed. Results. The glucose response to OGTT in fatty rats was indistinguishable from lean animals whereas the insulin response was 5x greater. IVGTT yielded the same pattern. The peak IR-GIP response to OGTT in 4 obese animals was 5000 pg/ml (~) compared to a ~ of 3000 in lean litter mates. The insulin response of the isolated perfused pancreas of obese rats to glucose was 3x greater than the response of lean animals, whereas the maximum in vitro response to 1 ng/ml GIP in fat animals was 18,000 vs. 7000 ~U/min from lean animals. Conclusions. Obese Zucker rats are normoglycemic, hyperinsulinemic and hyperGIPemic. An exaggerated insulin response to both OGTT and IVGTT indicates heightened B cell sensitivity. This is confirmed by in vitro perfusion studies in which glucose and GIP yielded a greatly magnified insulin response in obese vs. lean Zucker rats.
THE SATIATING POTENCY OF CHOLECYSTOKININ IS AN INVERSE FUNCTION OF THE INTENSITY OF SWEET TASTE. G.P. Smith and J. Bernz. E.W. Bourne Laboratory, N.Y. Hospital-Cornell Medical Center, White Plains, NY 10605, USA. To investigate the interaction between the positive effect of sweet taste and the inhibitory effect of cholecystokinin (CCK-8) on sham feeding, we prepared rats with chronic gastric fistulas. When the fistulas were opened after 18 h of food deprivation, rats (n=7) sham fed sucrose solutions almost continuously for 30 min. The intake of sucrose solution was a function of the percent concentration (w/v) of sucrose (Table i). Percent Sucrose Intake (mean mI±SE)
1.25 22±8.6
Table 1 2.5 5.0 35±6.3 40±5.0
i0.0 51±4.4
20.0 59±4.6
40.0 52±4.5
The inhibitory effect of CCK-8 (0.5, i, 2 and 4 ~g-kg -I) administered intraperitoneally just before presentation of 2.5, 5.0 or 10.0% sucrose solution was measured in 6 rats. The major result was that the inhibitory potency of CCK-8 (expressed as % inhibition of volume of intake) was an inverse function of the concentration of sucrose. For example, 2 ~g-kg -I CC~-8 inhibited the intake of 10% sucrose by 15%, inhibited the intake of 5% sucrose by 35%, and inhibited the intake of 2.5% sucrose by 54%. Since sham feeding eliminates the postingestive effects of sucrose, these results demonstrate that the satiating effect of CCK-8 is an inverse function of the intensity of sweet taste produced by sucrose.
CHRONIC BOMBESIN INJECTION CAN LEAD TO A PERSISTENT DECREASE OF FOOD INTAKE AND LOSS OF BODY WEIGHT IN RATS. David B. West, Robert H. Williams, Daren J. Braget and Stephen C. Woods. University of Washington, Seattle, WA. USA Although many gut hormones reduce the size of individual meals, few studies have administered these hormones over an extended period of time in an attempt to reduce body weight. Eight female Wistar rats were habituated to a schedule of food deprivation except for three ~0-minute sessions during the dark phase of the day/night cycle. Just prior to each session, the rats were given subcutaneous (sc) injections of saline followed by free access to