Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach
Open accessAbstract
Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.
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In addition to meal composition and size, the timing of macronutrient consumption during a meal seems to be a key regulator of postprandial hyperglycemia.
“Thus, in addition to meal composition and size, the timing of macronutrient consumption during a meal seems to be a key regulator of postprandial hyperglycemia [31,74].”
From Effects of diet, lifestyle, Chrononutrition and alternative dietary interventions on postprandial Glycemia and insulin resistance (2022) · cites this paper as [31]
The timing of carbohydrate ingestion (i.e., carbohydrate-last meal patterns) can markedly reduce postprandial glycemia by delaying gastric emptying, enhancing glucose-stimulated insulin release, and affecting insulin clearance.
“Moreover, it has been shown that the timing of carbohydrate ingestion (i.e., carbohydrate-last meal patterns) can markedly reduce postprandial glycemia by delaying gastric emptying, enhancing glucose-stimulated insulin release, and affecting insulin clearance [31,74].”
From Effects of diet, lifestyle, Chrononutrition and alternative dietary interventions on postprandial Glycemia and insulin resistance (2022) · cites this paper as [31]
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Flagged first, then by citations
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Cited by
Sorted by citations
Papakonstantinou, E., Oikonomou, C., Nychas, G., & Dimitriadis, G. D. (2022) · Nutrients · doi:10.3390/nu14040823 · Cited by 199 · see citing works
“The entrance of the remaining insulin into the peripheral circulation rapidly suppresses lipolysis in the adipose tissue and reduces plasma levels of NEFA; this facilitates the decrease of HGP/increase of glucose storage by insulin and permits the increase of insulin-stimulated glucose uptake by skeletal muscle for ox…”
BackgroundInfluentialSelf-citationInsulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance
Apostolopoulou, M., Lambadiari, V., Roden, M., & Dimitriadis, G. D. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnae032 · Cited by 90 · see citing works
Self-citationWei, H., Zhang, J., Cui, K., & Su, H. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1575580 · Cited by 13 · see citing works
- Authors
- Dimitriadis, G. D., Maratou, E., Kountouri, A., Board, M., & Lambadiari, V.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- University General Hospital Attikon (GR)
- University of Oxford (GB)
- Corresponding author
- Dimitriadis, George D.
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2021-01-06
- Volume
- 13
- Issue
- 1
- Pages
- 159
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC7825450
- OpenAlex
- W3118771552
- Cited by
- 241
- References
- 305
- Citations by year
- 2026: 55 · 2025: 63 · 2024: 42 · 2023: 34 · 2022: 37 · 2021: 10
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- glucose homeostasis, insulin resistance, postprandial blood glucose, hepatic glucose production, free fatty acids, adipose tissue, growth hormone, cortisol, glucagon, gastrointestinal hormones, gastric emptying, de novo lipogenesis, hyperglycemia, hyperinsulinemia, sleep
- MeSH terms
- Adipose Tissue, Blood Glucose, Fasting, Fatty Acids, Nonesterified, Gastric Emptying, Glucose, Homeostasis, Humans, Hyperglycemia, Hyperinsulinism, Hypoglycemia, Insulin, Insulin Resistance, Kidney, Liver, Muscle, Skeletal, Postprandial Period, Incretins, Meals
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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