Insulin Secretion
Conditions
Keywords
Incretins, GLP-1, GIP, hyperglycemic clamp, Glucagon
Brief summary
This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. However, there are important gaps in understanding incretin function that limit application of this system; this project will address several of these. A secondary, but critical aspect of this research is focus on inter-individual variation in the physiology of the incretin system. This is a novel direction for research in this field and is critical to advancing the concept of individualized medical care in diabetes by establishing whether there is a physiologic basis for predicting the existence of responders and non-responders to incretin therapies. Currently, we have described only Aim 1 from this grant in this protocol registration. While Aim 2 and 3 are described in the grant, Aim 1 will be conducted first and the results from this Aim and / or the publication of other results in the field may affect the approach to Aims 2 and 3.
Interventions
DRUGGIP infusion
after establishing a hyperglycemic clamp (target: 125 mg/dL) GIP will be infused
DRUGGLP-1 infusion
after establishing a hyperglycemic clamp (target: 125 mg/dL) GLP-1 will be infused
DRUGEx-9 infusion
Ex-9 infusion will be initiated at start of hyperglycemic clamp (target: 125 mg/dL)
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
David D'Alessio, M.D.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy adult volunteers * fasting plasma glucose value ≤ 95 mg/dL, measured at screening visit * HbA1c ≤ 5.9%, measured at screening visit
Exclusion criteria
* history of diabetes diagnosis, including gestational diabetes * presence of Type II diabetes mellitus among any first degree family members * rheumatoid arthritis * inflammatory bowel disease * unstable angina or uncompensated heart failure * pulmonary disorders including COPD and asthma * malabsorptive GI disease, such as celiac disease, or gastric bypass * significant hepatic disease * renal insufficiency (eGFR \< 60 mL/kg/min) * anemia (hematocrit \< 34%) as measured at screening visit * pregnancy * uncontrolled hypertension * consumption of daily medications that alter glucose metabolism or GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beta cell sensitivity | 30 minute infusion periods | Beta-cell sensitivity for each incretin will equal the slope of the insulin secretion rate divided by the specific incretin level (GLP-1 or GIP) |
Countries
United States
Outcome results
None listed