Cephalic-phase insulin secretion in normal and pancreatic islet-transplanted rats

Abstract

The ability of saccharin, in comparison with glucose and tap water, to elicit glycemia-independent neurally mediated insulin secretion was investigated in chronically catheterized, freely moving rats. Plasma glucose and insulin concentrations were measured continuously from venous blood with a sampling resolution of one per minute. In normal rats, 1 ml of 0.15% saccharin caused a significant rapid rise in peripheral plasma insulin levels lasting up to 5 min, without significant changes in glycemia. Tap water alone also induced a transient elevation in insulinemia but was much smaller than the saccharin-induced response. In streptozotocin diabetic rats bearing intrahepatic, presumably denervated islet isografts, these rapid insulin responses to oral saccharin and tap water stimulation were completely abolished, whereas the early insulin response to intravenous glucose was decreased by only about 30%. These results are consistent with the concept of gustatory and other oral sensory signals acting as triggers for neurally mediated insulin release.

Cephalic phase insulin secretion is KATP channel independent

“…Dextrin is digested in the oral cavity by amylase and its derivative maltose gives rise to sweet sensation in the mouth (Ninomiya et al 1998). Thus, voluntary feeding of dextrin is likely to evoke insulin secretion through sensing of sweetness in the cephalic phase of insulin secretion (Berthoud et al 1980). Interestingly, a small but significant increase in insulin secretion was induced by voluntary feeding of carbohydrate only in Kir6.2 K/K mice (Fig.…”

Autonomic regulation of islet hormone secretion - Implications for health and disease

“…They consist of three different pathways: first the afferent pathway activated by olfactory, visual, gustatory and oroparyngeal mechanical receptors, second the central integratory mechanism and third the efferent pathway [118]. In rats, a cephalic phase regulation of insulin secretion has been verified by insulin secretion seen during sham feeding [119,120], after food ingestion but before any significant increase in postabsorptive glycaemia is evident [121,122], and after ingestion of non-metabolisable food [123]. In humans, a cephalic phase regulating insulin secretion was first shown by an increased circulating insulin after imaginary food ingestion under hypnosis [124] and after the sight, smell and expectation of food in healthy subjects [125].…”

Anticipatory physiological regulation in feeding biology: Cephalic phase responses

“…Preventing the cephalic insulin phase response, for example through infusion of trimethaphan, which inhibits neurotransmission across autonomic ganglia results in both significantly higher peak blood glucose concentration and impaired reduction of glucose within the first hour post prandial ( Figure 3; Ahren and Holst, 2001),. Thus the absence of a cephalic phase insulin response compromises glucose control and can even lead to hyperinsulinemia (Berthoud et al, 1980). Administration of insulin immediately prior to or at the beginning of a meal, i.e.…”

“…Oral infusion of a glucose solution stimulates a cephalic phase insulin response in rats (e.g. Berthoud et al, 1980). Rats that ingested saccharine solutions displayed a reliable and dose dependent cephalic phase insulin response (Figure 4; Powley and Berthoud, 1985); ingesting sweetened solutions or sucking on sweetened tablets do not reliably initiate insulin secretion in human subjects (Bruce et al, 1987;Abdallah et al, 1997).…”

“…Finally, in rodent models in which the pancreatic ß cells have been destroyed, and new ß cells transplanted such that they lack innervation by the vagus nerve, the reactive insulin secretion to increases in blood glucose is still intact, but the cephalic phase insulin secretion is absent (e.g. Berthoud et al, 1980). Many cephalic phase responses are intrinsic, and appear to require only brain stem function and are not dependent on forebrain structures.…”