Investigating the link between taste perception and circulating levels of of insulin (and related metabolic hormones): a pilot study.

Olfaction and gustation are important sensory modalities for locating food and
for determining which foods to ingest, as they indicate the quality, safety,
and palatibility of the food. Taste sensations arise from stimulation of the
gustatory receptors located within the oropharyngeal mucosa. Taste begins with
molecular signaling events involving receptors at the surface membranes of
modified epithelial cells, which share many characteristics with neurons. The
taste cells in the tongue are located in specialized structures, known as taste
buds. Groups of taste buds are organized in papillae and each papilla contains
approximatley 3 to 5 taste buds. It is becoming apparent that there is a
strong link between taste perception and metabolic control. In fact, it seems
that endocrine signaling in the taste buds of the tongue is likely to influence
food intake, satiety and the general metabolic state. For example, several
hormones that are crucial for the control of energy balance and appetite
control have now been found to be present in taste buds and are thought to
exert a strong local effect on taste sensitivity. These hormones include:
glucagon-like peptide 1 (GLP-1), vasoactive intestinal peptide (VIP), ghrelin,
glucagon, cholecystokinin, and neuropeptide Y (NPY).
The presence and functionality of metabolic hormones in the tongue suggests
that the proper maintenance of olfactory and gustatory sensations is critical
for managing adequate energy intake. Reinforcing this proposition, it has
recently been demonstrated that alterations in flavor perception are indeed
linked to metabolic dysfunction. Appetite hormones and their receptors in the
tongue are likely to control taste sensitivity, which may then subsequently
alter food preferences and food intake. For example, leptin, an anorexigenic
hormone, is produced by adipocytes and plays a role in controlling food intake
by acting upon leptin receptors expressed in the hypothalamus. Recent findings
however have demonstrated that leptin receptor is also expressed on taste buds
and that peripherally circulating leptin can activate these receptors to
significantly attenuate sweet taste sensitivity.
It is clear from our research that numerous appetite hormones are present
within the tongue and that there is a highly complex and organized interplay
between peripheral hormones and tongue hormones. The interplay between these
systems modulates not only gustatory function but also whole-body physiological
functions, such as metabolic control and energy homeostasis. Many of the exact
functional roles of these hormones remain to be established because we have
only reached the tip of the iceberg with regards to elucidating how these
hormones also modulate gustation. From the functional roles that have been
established so far, it is becoming apparent that many hormones retain similar
functional mechanistic actions at different target organs. The prime example
so far is GLP-1, which modulates multiple coordinated energy-regulating
programs, i.e. circulatory glycemic control in the periphery and sweet taste
perception in the tongue. There seems to be a conservation of function through
multiple layers of physiological systems, which from an evolutionary standpoint
would create a more synergistic and efficient homeostatic and sensorial
system. By gaining a better understanding of how these endocrine functions are
conserved throughout different physiological modalities, we will obtain a
better appreciation of how complex higher-order endocrine systems are
organized. A greater understanding of the functional structure of these
systems will facilitate a more efficient pharmacological exploitation of them,
to combat conditions such as obesity and Type 2 diabetes. So far, research in
this area is in its infancy and we hope that the next few years will see an
exponential improvement in our knowledge of hormonal activity in the tongue.
Currently, it is not clear how, in humans, taste sensitivity could be linked to
peripheral metabolic function. Clinical studies are needed to establish
whether non-, medium-, and super-taster ability is linked to peripheral
metabolic control. A greater understanding of the link between taste
sensitivity and metabolic function could lead to novel tongue-targeted
therapeutics for the treatment of obesity, metabolic syndrome, and Type 2
diabetes.

We propose that there will be a link between taste sensitivity and overall
metabolic function. We hypothesize that non-tasters, medium-tasters and
super-tasters will have different levels of metabolic hormones in their general
circulation. Our study will contain two arms: one which contains healthy
subjects that fall into one of the three taste sensitivity groups (non-tasters
and tasters) and a second which will contain subjects presenting with Type 2
diabetes, a condition that may involve circulatory alterations in
taste-modifying energy-regulatory hormones.

This study will take 6 months and we will adhere to the following time-line:
Step 1. Recruitment of subjects (month 1)
10 subjects currently being treated by the Onze Lieve Vrouwe Gasthuis for Type
2 diabetes will be recruited by their physician. Additionally, healthy control
subjects that are non-tasters (n = 15) and tasters (n = 15) will be recruited
by the Better Immune System Foundation.
Step 2. Data and blood/saliva collection (month 1-2)
Physicians at the Onze Lieve Vrouwe Gasthuis will take measurements form the
participating study subjects and the following parameters will be collected:
interview/questionnaire, physical measurements (body weight), taste tests,
tongue images, and collection of plasma and saliva samples.
Step 3. Saliva and plasma analysis (month 3-4)
The levels of the metabolic hormones in plasma and saliva will be analyzed by
the National Institute on Aging.
Step 4. Perception and behavior analysis (month 3-4)
Perception of taste and olfaction will be evaluated by the Better Immune System
Foundation and will be correlated to eating habits and general behavior.
Step 5. Joint analysis and conclusions (month 5-6)
The National Institute on Aging, Onze Lieve Vrouwe Gasthuis, and the Better
Immune System Foundation will analyze the combined data and publish the
findings.

There are no known risks for these procedures. The taste and smell strips could
potentially be perceived as unpleasant by some subjects. The blood collection
could potentially have these following effects: feelings of weakness, mild
pain, irritation around the injection area, and a low chance of infection. The
total procedure takes approximately 15 minutes