Cephalic phase metabolic responses in normal weight adults

doi:10.1016/0026-0495(87)90106-5

Metabolism

Volume 36, Issue 8, August 1987, Pages 721-725

https://doi.org/10.1016/0026-0495(87)90106-5 Get rights and content

Abstract

The presence and physiologic importance of cephalic phase insulin release in humans remains controversial. The aim of these studies was to determine whether cephalic phase insulin release could be demonstrated in normal weight subjects and whether it would be associated with changes in blood glucose, free fatty acid, and pancreatic polypeptide levels. The studies were followed by a hyperglycemic clamp to determine whether cephalic responses would alter overall glucose disposal or glucose-stimulated insulin secretion. In all, 17 subjects were studied on two occasions with and without (control study) presentation of food stimuli. Tease-feeding alone (n = 6), or the administration of a sweet taste alone (aspartame, n = 5) failed to stimulate cephalic responses. However, the presentation of the combined stimuli (tease meals plus sweet taste, n = 7) resulted in a significant fall (P < .005) in blood glucose levels and a variable rise in serum insulin (% insulin rise 38 ± 15%, P < .05) and C-peptide levels (7 ± 6%, NS) within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly (r = .90, P < .01) with a score of the subjective response to the food and taste. There were strong negative correlations between the individual cephalic insulin responses and the initial blood glucose increment following the start of the dextrose infusion (r = .87, P < .02) and also between the cephalic insulin responses and an index of glucose metabolism (mean blood glucose increment/mean dextrose infusion rate) during the first 30 minutes of the hyperglycemic clamp (r = −.87, P < .02). We conclude that cephalic phase metabolic responses can be elicited in normal weight humans using a combination of food-associated stimuli. Cephalic responses include a prompt rise in insulin and a seemingly independent fall in blood glucose with the magnitude of the latter proportional to the subjective perception of the stimuli. Cephalic phase responses have a restraining effect on the early blood glucose rise induced by an intravenous glucose load and may have a role in postprandial glucoregulation.

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Although food deprivation (i.e., fasting) may influence CPIR magnitude [108], this variable is not controlled consistently across studies. Some investigators fasted subjects overnight [e.g., [26],[32],[56],[99]], whereas others did so for 3–4 h [e.g., [8],[14],[55],[69],[102]]. Given that the metabolic changes associated with a meal can last up to five hours [109], it is generally recommended to implement a longer fasting period prior to measuring CPIR in order to limit the influence of nutrients and metabolic processes from previous meals.
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Food anticipatory hormonal responses: A systematic review of animal and human studies
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Food anticipatory hormonal responses (cephalic responses) are proactive physiological processes, that allow animals to prepare for food ingestion by modulating their hormonal levels in response to food cues. This process is important for digesting food, metabolizing nutrients and maintaining glucose levels within homeostasis. In this systematic review, we summarize the evidence from animal and human research on cephalic responses. Thirty-six animal and fifty-three human studies were included. The majority (88 %) of studies demonstrated that hormonal levels are changed in response to cues previously associated with food intake, such as feeding time, smell, and sight of food. Most evidence comes from studies on insulin, ghrelin, pancreatic polypeptide, glucagon, and c-peptide. Moreover, impaired cephalic responses were found in disorders related to metabolism and food intake such as diabetes, pancreatic insufficiency, obesity, and eating disorders, which opens discussions about the etiological mechanisms of these disorders as well as on potential therapeutic opportunities.
Insulin and insulin analogs as antidiabetic therapy: A perspective from clinical trials
2021, Cell Metabolism
The discovery of insulin in 1921 and the progress achieved in the ensuing century highlight the promise and challenge of biochemically modifying the molecule to achieve optimization of its delivery and therapeutic efficacy. Normal endogenous insulin secretion consists of a highly orchestrated physiologic loop wherein multiple metabolic signals trigger the pancreatic β cells to secrete the precise amount of insulin into the portal system required to maintain euglycemia. Accordingly, in the treatment of diabetes, attempting to replicate this complex physiology with exogenous insulin therapy given subcutaneously presents a clinical challenge. In this context, recombinant DNA-based technology has enabled the development of insulin analogs that have been specifically designed to confer advantageous pharmacodynamic features that can better mimic endogenous insulin secretion. In this review, we discuss the development of the most widely available insulin preparations and provide evidence-based insight into their use in clinical practice.
Evidence for cephalic phase insulin release in humans: A systematic review and meta-analysis
2020, Appetite
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A random effects meta-analysis with an added moderator for the type of stimulus presentation (one, two, three or four sensory qualities combined), found that the type of presentation significantly influenced effect size estimates for cephalic phase insulin release (F(3, 73) = 3.94, p = 0.012). Concordant with what has long been suggested in the literature (Bruce et al., 1987), the presentation of a food stimulus to all sensory qualities at the same time elicited the strongest response, with an effect size estimate increase of 0.84 [95%CI 0.13, 1.55] p = 0.021 [Fig. 4A–B]. Furthermore, we tested the influence of the type of stimulus offered (liquid vs. solid formulation).
The initial release of insulin in response to food stimuli acting on receptors in the head and oropharynx is called the cephalic phase of insulin secretion. Insulin has been shown to act centrally to regulate food intake and glucose metabolism and the cephalic phase of insulin secretion may contribute to these functions. Though well documented in laboratory animals, the existence of cephalic phase insulin release in humans has recently come into question. We therefore performed a systematic review and meta-analysis of studies of cephalic phase insulin release in humans. Efficacy outcomes included any change in circulating insulin levels in healthy human volunteers post any food stimulus as compared to baseline or control in a time period of no longer than 10 min. Primary outcome: The overall pooled effect size estimate for cephalic phase insulin release was 0.47 [0.36, 0.58] p-value <0.0001. Secondary outcomes: A random effects meta-analysis with an added moderator for type of stimulus presentation (one, two, four or five sensory qualities) and type of stimulus offered (liquid, solid formulation) also significantly influenced results p = 0.0116 and p = 0.0024 respectively, while sex had no significant effect. Sensitivity Analysis: More restrictive analyses only including studies that used non-ingestive stimuli (p = 0.0001), or studies that reported insulin values within 5 min post stimulus presentation (p < 0.0001) still showed significant positive overall effect size estimates. In summary, our analysis shows that there is evidence for the presence of cephalic phase insulin secretion in humans. Secondary analyses suggest that the type and presentation of stimulus may significantly influence cephalic phase insulin secretion, while sex had no significant effect on cephalic phase insulin secretion.
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2019, Nutrition Research
Citation Excerpt :
Importantly, in the Asp trial, rinsing with GS solution did not affect all physiological responses both during and after the prandial phase, as opposed to the results of the Glu trial. Previous studies have reported that modified sham feeding or oral ingestion involving aspartame solution could not elicit cephalic-phase insulin responses (CPIRs) in humans [23-25]. CPIRs contribute to the prevention of postprandial hyperglycemia.
Previously, we reported that oral stimulation with Gymnema sylvestre (GS), a plant that selectively suppresses sweet taste sensation in humans, delayed gastric emptying and glycemic response during and after oral glucose ingestion. It is unclear whether these responses are triggered by sweet taste sensing per se. We tested the hypothesis that the effects of sweet taste sensing involving a low-energy sweetener, aspartame, alters gastric emptying, blood glucose, and plasma insulin responses during and after the prandial phase. Nine participants rinsed their mouths with either 25 mL of water (control) or a 2.5% GS solution, and then ingested 200 g (50 g × four times) of either 0.09% aspartame or 15% glucose solution containing 100 mg of ¹³C-sodium acetate. Gastric emptying was measured with a ¹³C breath test. Blood glucose and plasma insulin were measured at baseline as well as during and after ingestion of the sweet solutions. Decreased subjective sweet taste intensity was observed in the GS group for both the aspartame and glucose trials. In the aspartame trial, no measurements showed significant differences between either group. In the glucose trial, gastric emptying was delayed in the GS group compared to controls. In the initial phase, both during and after glucose ingestion in the glucose trial, blood glucose and plasma insulin responses were lower in the GS group than the controls. The presence or absence of sweet taste-sensing involving glucose had a significant effect on gastric emptying and glycemic metabolism, both during and after the prandial phase, as opposed to the effects involving aspartame.

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^☆: Supported by grants from the NH and MRC (Australia).

¹: D.G. Bruce is the recipient of a CSL-Novo Scholarship.

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Cephalic phase metabolic responses in normal weight adults☆

Abstract

Metabolism

Brain Res

Preabsorptive insulin release and hypoglycemia in rats

Am J Physiol

The mechanism of insulin secretion after oral glucose administration. II. Reflex insulin secretion in conscious dogs bearing fistulas of the digestive tract by sham-feeding of glucose or tap water

Diabetologia

Plasma insulin levels during imaginary food ingestion under hypnosis

Cephalic phase of insulin secretion in obese adolescents

Diabetes

Effect of cephalic-vagal stimulation on insulin, gastric inhibitory polypeptide, and pancreatic polypeptide release in humans

J Clin Endocrinol Metab

Fall in plasma content of free fatty acids associated with sight of food

N Engl J Med

Central nervous system regulation of liver and adipose tissue metabolism

Diabetologia

The role of the ventromedial hypothalamic area in periprandial glucoregulation

Life Sci