Ketones and Insulin: A Paradoxical Interplay With Implications for Glucose Metabolism.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic, preclinical, and human literature without systematic methodology
PubMed 40585886 · doi:10.1210/jendso/bvaf101
What was done
This narrative review synthesized historical and contemporary literature exploring the metabolic and signaling interplay between ketone bodies (particularly exogenous beta-hydroxybutyrate) and insulin secretion across isolated pancreatic islets, rodent models, and human subjects.
What was found
The abstract reports no quantitative values or effect sizes. Historically, chronic ketone exposure was observed to initially stimulate insulin secretion but eventually cause beta-cell exhaustion and hyperglycemia. Recent evidence confirms that ketones exert an insulin-stimulatory effect in islets, animals, and humans, though this effect depends on exposure duration and ambient glucose availability, partially mediating the glucose-lowering effect of exogenous ketones.
Why it matters
It highlights a physiological paradox where ketone bodies act as insulinogenic signaling molecules despite endogenous ketosis naturally occurring during low-insulin states, informing therapeutic exploration of exogenous ketones in dysregulated glucose metabolism.
Limits
The abstract provides no quantitative data, sample sizes, or standardized outcome metrics. As a narrative review, it lacks systematic search criteria, quality appraisal, and meta-analytic synthesis, and much of the underlying mechanistic data derives from non-human models.