Olive oil before carbs blunts early blood sugar rise in mice
Edited by Swati Mestri, reviewed by Robert Egan
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| Olive oil administered before carbohydrates elicits early glucagon and GLP-1 responses that act in a partially redundant manner and, with involvement of vagal pathways, slow gastric emptying and attenuate the early post-meal glucose. |
In treating diabetes, postmeal elevation of glucose levels
is an important therapeutic target. Existing clinical studies indicate that
eating vegetables, protein or fat before carbohydrates can moderate a postmeal
rise in blood glucose, pointing to the potential of meal sequencing as a simple
and sustainable dietary strategy.
Scientists have often attributed the benefits of this
strategy to slower gastric emptying and greater secretion of incretin hormones,
such as GLP-1, that decrease blood glucose levels. However, the roles that gut
and pancreatic hormones, as well as neural pathways, play in this process have
remained less understood.
This motivated an international team of researchers to
investigate how the timing of fat intake influences glucose levels, hormone
secretion and gastric emptying. Their study is published in the journal Diabetes.
"Our group has long been interested in practical
dietary approaches that people can continue in everyday life," says
corresponding author Daisuke Yabe of Kyoto University. "Meal sequencing is
appealing because it merely changes how a meal is eaten rather than requiring
people to avoid entire food groups."
Testing fat intake before and after glucose
The team used mice in their investigation, first having them
fast overnight. The mice were then divided into three groups: one received
water followed by glucose, another received olive oil followed by glucose 15
minutes later, and the final group received glucose followed by olive oil 15
minutes later.
After feeding the mice accordingly, the researchers measured
blood glucose, plasma insulin, glucagon, GIP and GLP-1 levels. The team also
gave the mice acetaminophen and estimated gastric emptying by measuring blood
acetaminophen levels after oral administration.
The scientists then repeated this experiment in a few other
groups of mice, including those with type 2 diabetes and those lacking the
GLP-1 receptor. Additional experiments also included inhibiting glucagon or
GLP-1 signaling, performing bilateral subdiaphragmatic vagus nerve ligation and
testing other dietary fats to confirm that responses were not specific to olive
oil.
Fat first slows the glucose rise
These test results revealed that giving mice olive oil
before rather than after glucose reduced an early rise in blood glucose levels
and slowed gastric emptying. Consuming fats before glucose also increased early
secretion of glucagon, GIP and GLP-1, and all of these beneficial effects were
retained in mice with type 2 diabetes and severe insulin deficiency.
The researchers observed that inhibiting either glucagon or GLP-1
signaling alone did not attenuate the glucose-lowering effect of the olive
oil preload, whereas combined inhibition did. They also found that glucagon
signaling, which is best known for raising blood glucose, contributes to the
glucose-lowering response of an olive oil preload in mice. The experiments
involving vagus nerve ligation also suggested that vagal pathways contribute to
these responses.
A rationale for human meal-sequencing trials
By providing a physiological explanation for the influence
of nutrient order on postmeal glucose levels, this study strengthens the
rationale for testing practical meal-sequencing strategies in people with and
without diabetes.
"Our findings suggest that the order in which nutrients
reach the gut can engage a coordinated hormone-nerve response that changes how
quickly the stomach delivers glucose to the intestine," says Yabe.
Publication details
Olive Oil Before Oral Glucose Delays Gastric Emptying and
Lowers Glycemia Through Partially Redundant Glucagon and GLP-1 Signaling in
Mice, Diabetes (2026). DOI: 10.2337/db26-0531
Journal information: Diabetes