PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria

Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria. Research Design/Plan: After screening, eligible subjects will receive 2 measurements of endogenous glucose production with a prime-continuous infusion of 3-3H-glucose. Each measurement will be performed on a separate day in random order after a 10-12 hour overnight fast and will last 8 hours (from 6 AM to 2 PM). After a 3-hour tracer equilibration period, each subject will receive one of the following medications in random order: (i) placebo and (ii) dapagliflozin 10 mg. Following the test medication at 9 AM, blood samples will be drawn every 20 minutes for an additional 5 hours and plasma glucose, insulin, C-peptide, glucagon, catecholamine concentrations and tritiated glucose sp act will be measured. Methods: Visit 1: Screening Visit 2: Endogenous Glucose Production Measurement (EGP) Visit 3: After completing the first EGP measurement, subjects will return to the Diabetes Research Unit for the second study.