GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.
Accumulating evidence suggests that in rodents and humans GLP-1 is synthesized within islets and may act locally in a paracrine fashion. Indeed, mice with genetic loss of intra-islet GLP-1 exhibit decreased insulin secretion and impaired response to metabolic stressors. 'Pancreatic' GLP-1 may contribute to the effects of DPP-4 inhibitors in rodents and humans. Antagonism of GLP1R with exendin-9,39 during fasting impairs the islet cell response to an I.V. glucose challenge. Islet GLP-1 content is increased in T2DM and in islets from non-diabetic humans exposed to hyperglycemia and Free Fatty Acids. These observations imply that paracrine GLP-1 secretion supports islet function in the presence of glucolipotoxicity. In this experiment we will examine the role of endogenous GLP-1 secretion in people with and without T2DM and during β-cell stress induced by FFA elevation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
23
Saline infused during the study
Exendin-9,39 infused during the study
Saline infused during acute insulin resistance
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39
Concentrations of glucagon Measured by immunoassay over the -30 to 0 minutes of study. On one study day subjects received saline, on the other exendin-9,39. The infusion commenced at -120 minutes.
Time frame: Average concentration over the -30 to 0 minutes of study
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Exendin-9,39 infused during acute insulin resistance