The Effect of Glycemic Control and of GLP-1 Receptor Agonism on Islet GLP-1 in People
Mayo Clinic
Summary
The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. There is evidence that α-cell proglucagon processing is subject to paracrine regulation by the β-cell3. It is unclear if the effects of GLP1R agonism on islet GLP-1 differ in Type 1 diabetes (T1DM) compared to T2DM. This experiment will examine the effect of glycemic control ± a GLP1R agonist on islet GLP-1 in people with (T2DM) and without (T1DM) β-cells.
Description
The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. This supports other evidence (rodents and humans) that through the (inducible) expression of a prohormone convertase (PC-1/3), the α-cell can process proglucagon to intact GLP-15,6. 'Islet' or 'pancreatic' GLP-1 acts in a paracrine fashion to regulate insulin (basal and 1st phase) and glucagon secretion. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased express…
Eligibility
- Age range
- 25–70 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Type 1 or type 2 diabetes treated with insulin Exclusion Criteria: 1. Age \< 25 or \> 70 years. 2. HbA1c \> 10.0% 3. For female subjects: positive pregnancy test at the time of enrollment or study 4. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy. 5. Prior use of GLP-1 receptor agonists in the previous year. 6. Active systemic illness or malignancy. 7. Symptomatic macrovascular or microvascular disease.
Interventions
- DrugLiraglutide Pen Injector
Liraglutide 0.6mg
- OtherSaline Injections
Saline in syringes to serve as placebo for single blind study
Location
- Mayo Clinic in RochesterRochester, Minnesota