Feast and Famine: Critical Role of Glucocorticoids with Insulin in Daily Energy Flow
Abstract
The hypothesis proposed in this review is that normal diurnal rhythms in the hypothalamic-pituitary-adrenal (HPA) axis are highly regulated by activity in medial hypothalamic nuclei to effect an interaction between corticosteroids and insulin such that optimal metabolism results in response to changes in the fed or fasted state of the animal. There are marked diurnal rhythms in function of the HPA axis under both basal and stress conditions. The HPA axis controls corticosteroid output from the adrenal and, in turn, forward elements of this axis are inhibited by feedback from circulating plasma corticosteroid levels. Basal activity in the HPA axis of mammals fed ad lib peaks about 2 h before the peak of the diurnal feeding rhythm, and is controlled by input from the suprachiasmatic nuclei. The rhythm in stress responsiveness is lowest at the time of the basal peak and highest at the time of the basal trough in the HPA axis activity. There are also diurnal rhythms in corticosteroid feedback sensitivity of basal and stress-induced ACTH secretion which peak at the time of the basal trough. These rhythms are all overridden when feeding, and thus insulin secretion, is disrupted. Corticosteroids interact with insulin on food intake and body composition, and corticosteroids also increase insulin secretion. Corticosteroids stimulate feeding at low doses but inhibit it at high doses; however, it is the high levels of insulin, induced by high levels of corticosteroids, that may inhibit feeding. The effects of corticosteroids on liver, fat, and muscle cell metabolism, with emphasis on their interactions with insulin, are briefly reviewed. Corticosteroids both synergize with and antagonize the effects of insulin. The effects of stress hormones, and their interactions with insulin on lipid and protein metabolism, followed by some of the metabolic effects of injury stress, with or without nutritional support, are evaluated. In the presence of elevated insulin stimulated by glucocorticoids and nutrition, stress causes less severe catabolic effects. In the central nervous system, regulation of function in the HPA axis is clearly affected by the activity of medial hypothalamic nuclei that also alter feeding, metabolism, and obesity in rats. Lesions of the arcuate (ARC) and ventromedial (VMN) paraventricular (PVN) nuclei result in obesity and hyperactivity in the HPA axis. Moreover, adrenalectomy inhibits or prevents development of the lesion-induced obesity. There are interactions among these nuclei; one mode of communication is via inputs of neuropeptide Y (NPY) cells in the ARC to the VMN, dorsomedial nuclei, and PVN.(ABSTRACT TRUNCATED AT 400 WORDS)
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Stress is associated with increased appetite.
“Similarly, stress has been shown to be associated with increased appetite (Dallman et al., 1993)”
From The impact of stress on students in secondary school and higher education (2020) · cites this paper as Dallman et al., 1993
Experimentally increasing late-afternoon and early-evening cortisol through hydrocortisone administration induces insulin resistance the following day.
“In fact, experimentally increasing late-afternoon and early-evening cortisol through hydrocortisone administration induces insulin resistance the following day [69, 73, 74].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [69]
Hypercortisolemia during the late-afternoon and early-evening is harmful, and is believed to cause insulin resistance observed with advanced age, impair physical performance, and trigger neurocognitive deficits.
“These findings are highly relevant because hypercortisolemia during the late-afternoon and early-evening is harmful, and is believed to cause the insulin resistance observed with advanced age [60, 69, 70], impair physical performance [71] and trigger neurocognitive deficits [72].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [69]
Administration of glucocorticoids to bolster late afternoon and early evening cortisol levels induces insulin resistance through post-receptor mechanisms.
“Administration of glucocorticoids to bolster cortisol levels in the late afternoon and early evening also induces insulin resistance [69, 73, 74] through post-receptor mechanisms [90–92].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [69]
Raised cortisol concentrations in the evening are thought to contribute to age-related insulin resistance.
“Raised cortisol concentrations in the evening are thought to contribute to age-related insulin resistance [55], [56].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [55]
Circadian misalignment may lead to central and peripheral deleterious consequences, such as memory deficit and insulin resistance.
“Circadian misalignment may lead to central and peripheral deleterious consequences, such as memory deficit and insulin resistance [69–71].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [70]
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- Authors
- Dallman, M. F., Strack, A. M., Akana, S. F., Bradbury, M. J., Hanson, E. S., Scribner, K. A., & Smith, M.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 1993-10
- Volume
- 14
- Issue
- 4
- Pages
- 303-347
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W1971922927
- Cited by
- 796
- References
- 0
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 21 · 2022: 15 · 2021: 20 · 2020: 22 · 2019: 22 · 2018: 13 · 2017: 13 · 2016: 30 · 2015: 26 · 2014: 27 · 2013: 20 · 2012: 33
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK28172)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoids, insulin, hypothalamic-pituitary-adrenal axis, diurnal cycle, feeding behavior, stress hormones, corticosteroid feedback, ACTH secretion, arcuate nucleus, neuropeptide Y, obesity, energy metabolism, lipid metabolism, protein metabolism, catabolism, adrenalectomy, body composition
- MeSH terms
- Animals, Circadian Rhythm, Eating, Energy Metabolism, Fasting, Feeding Behavior, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Insulin, Pituitary-Adrenal System, Stress, Physiological, Rats
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