Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.
The interaction between α-cell and β-cell function to regulate fasting glucose is incompletely understood. This is an important gap in our knowledge as fasting glucose contributes disproportionately to HbA1c and the microvascular complications of type 2 diabetes (T2DM). The regulation of fasting glucose in health and disease is relatively understudied. Insulin and glucagon should regulate glucose reciprocally through direct interaction; insulin restrains α-cell secretion while glucagon directly stimulates β-cell secretion. In addition, there are indirect interactions via changes in glucose. Glucagon increases endogenous glucose production (EGP) increasing glucose (and insulin secretion). Conversely, insulin stimulates glucose disappearance (Rd) and suppresses EGP, lowering glucose (and stimulating glucagon). However, this does not appear to occur uniformly in prediabetes. For example, in impaired fasting glucose (IFG), glucagon secretion rate (GSR) is inappropriate for the prevailing glucose. This is not accompanied by reciprocal changes in insulin secretion rate (ISR). Variability in the hepatic response to glucagon and to insulin further compound the dysregulation of fasting glucose. The net effect of these variables is unknown. This experiment is intended to test the hypothesis that impaired glucagon-induced insulin secretion contributes to fasting hyperglycemia in IFG.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
Mayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGChange in beta-cell responsivity induced by glucagon
The beta-cell responsivity observed during glucagon infusion will be compared to that observed during glucose infusion
Time frame: Beta-cell responsivity will be calculated as the gradient of the relationship between glucose concentrations and insulin secretion rate during the study day over the 4 hours (0 to 240 minutes) of the study
change in endogenous glucose production induced by glucagon
The endogenous glucose production observed during glucagon infusion will be compared to that observed during glucose infusion
Time frame: The rate of endogenous glucose production at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared
change in glucose disappearance induced by glucagon
The glucose disappearance observed during glucagon infusion will be compared to that observed during glucose infusion
Time frame: The rate of glucose disappearance at the end of the study (240 minutes) will be expressed as a percentage of that at the beginning of the study (0 minutes). The % change for each study day will then be compared
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
60