A Study of the Function of Hormones Present In Taste Buds

Cephalic phase of insulin secretion is regulated by autonomic and endocrine responses to
food-related sensory stimulation such as sight, smell, and taste. Human taste perception
comprises of at least five distinct qualities: bitterness, saltiness, sourness, sweetness,
and umami, the sensation elicited by glutamate, commonly found in protein (meat, fish, and
legumes) and flavor enhancer such as monosodium glutamate (MSG).

Both the sweet and umami taste stimuli had been shown to illicit cephalic-phase insulin
release in rats. Oral sensory stimulation in human with modified sham feeding (MSF where food
is smelled, chewed, but not swallowed) had been shown to enhance insulin release during the
cephalic phase, lower postprandial glucose level, and improve glucose tolerance in healthy
subjects. The loss of pre-absorptive insulin response has been shown to impair glucose
tolerance. Furthermore, patients with type 2 diabetes and their first degree relatives had
been shown to have impairment of sweet taste.

Recently, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) have been found in the taste
cells located in the taste buds of mice (unpublished data). These new findings raise several
interesting questions of whether strict tasting of food without ingestion may stimulate
secretion of GLP-1 and PYY from the taste cells, whether their secretion is involved in the
afferent input of the cranial nerves, and whether this secretion is impaired in obesity and
in patients with pre-diabetes or type 2 diabetes. We also want to investigate whether
different tastants, such as sweet versus umami, and different food contents such as percent
fat versus carbohydrate compositions, would elicit different hormonal responses.

- INCLUSION CRITERIA:

1. Males or females age 20 to 50

2. body weight > 50 kg (110 pounds)

3. Group A

1. BMI < 25 kg/m(2)

2. healthy

4. Group B

1. BMI greater than or equal to 30 kg/ m(2)

2. healthy

5. Group C

1. Pre-diabetes

2. Pre-diabetes is defined as having either impaired fasting glucose (IFG)
(fasting plasma glucose (FPG) greater than or equal to100 mg/dl but < 126
mg/dl) and/or impaired glucose tolerance (IGT) (2-hour OGTT glucose greater
than or equal to140 mg/dl but < 200 mg/dl).

3. BMI greater than or equal to 30 kg/m(2)

6. Group D

1. Type 2 diabetes (on diet or oral agents management only except for
thiazolidinediones)

2. Type 2 diabetes is defined as FPG 126 mg/dl and/or 2-hour OGTT glucose

200

3. BMI greater than or equal to 30 kg/m(2)

7. Screening laboratory evaluations with no significant abnormal results:

1. comprehensive metabolic panel

2. complete blood count with differential and platelets

3. fasting plasma glucose < 100 mg/dl for healthy groups only (Group A and B)

4. 2-hour 75-gram OGTT glucose < 140 mg/dl for healthy groups only (Group A and
B)

5. Negative pregnancy test for women of child-bearing potential

8. Able to complete an informed consent

EXCLUSION CRITERIA:

1. Pregnancy (pregnancy has been shown to be associated with decrease in insulin
sensitivity

2. Group A and B subjects cannot have FPG greater than or equal to 100 mg/dl or 2-hr OGTT
greater than or equal to 140 mg/dl

3. Group D subjects cannot have FPG > 240 mg/dl during the screening visit

4. Group D subjects cannot have their morning fasting finger-stick glucose > 240 mg/dl
during the 5 days (3 days for glucophage) prior to the visit when their oral
hypoglycemic agent(s) are discontinued

5. Subjects with type 2 diabetes on insulin therapy

6. Hematocrit < 36% for women and < 38% for men

7. Peanut allergy

8. Presence of other medical conditions that could affect glucose homeostasis

9. Use of medications known to impair glucose homeostasis (i.e., amiloride shown to
inhibit certain taste responses in hamsters)

10. History of liver or renal disease

11. History of gastrointestinal or endocrine disorders except for treated hypo- or
hyperthyroidism

12. Long-term glucocorticoid use (over one month), or other immunosuppressive agents
within the past 5 years