Cephalic phase, reflex insulin secretion neuroanatomical and physiological characterization

Abstract

Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that the CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.

GLUT2, glucose sensing and glucose homeostasis

“…Examples of such glucose-sensing systems include the taste bud cells. These express the sweet taste receptors (T1R2/T1R3) [1], which detect the presence of sugar in the food and initiate nervous responses to control the cephalic phase of insulin secretion, as well as food preference [2,3]. In hepatocytes, high glucose concentrations activate the transcription factor known as carbohydrate response elementbinding protein (ChREBP), a key inducer of glycolysis and lipogenesis [4].…”

Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight

“…6,7 This variability has enabled investigators to identify measures in adult rats, at normal body weight, that can accurately and reproducibly differentiate distinct subgroups that are obesity-prone (OP) or obesity-resistant (OR). These markers of obesity include initial weight gain during the first few days on a high-fat diet, 1,8 levels of leptin after a single high-fat meal in rats maintained on a lab chow diet, 9 meal-induced release of insulin 10 and fasting levels of triglycerides or basal growth hormone secretion in rats on chow. 11,12 While still at normal weight, the OP rats are found to exhibit a phenotype that has similarities to that seen in adult rats after they have become obese.…”

Vagotomy Suppresses Cephalic Phase Insulin Release in Sheep

“…1B and D), the cephalic phase insulin secretion, is well documented in non-ruminants including humans (Strubbe & Steffens, 1975;Berthoud et al 1980Berthoud et al , 1981Berthoud & Jeanrenaud, 1982;Strubbe, 1992;Teff et al 1995) and in ruminants (Bassett, 1974;Bhattacharya & Alulu, 1975;Chase et al 1977;Porter & Bassett, 1979;Vasilatos & Wangsness, 1980;Faverdin, 1986). However, the observation (Figs 1 and 2) that vagotomy suppresses the secretion of insulin that occurs immediately after the start of eating, has not been reported previously for ruminants.…”

“…CPIR is well documented in non-ruminants, including humans (Berthoud et al 1980(Berthoud et al , 1981Berthoud & Jeanrenaud, 1982;Strubbe, 1992;Teff et al 1995) and ruminants (Bassett, 1974;Bhattacharya & Alulu, 1975;Chase et al 1977;Vasilatos & Wangsness, 1980;Faverdin, 1986). It has been suggested that CPIR is one of a group of physiological responses that occur after activation of the vagus nerve through food-related sensory stimulation (Berthoud et al 1981;Taylor & Feldman, 1982).…”

“…It has been suggested that CPIR is one of a group of physiological responses that occur after activation of the vagus nerve through food-related sensory stimulation (Berthoud et al 1981;Taylor & Feldman, 1982). It has been shown that food-related CPIR in rats is mediated through reflex centres in the hypothalamus (Niijima et al 1990;Niijima, 1991).…”