Introduction and Objective: In a large animal model of type 2 diabetes (T2D), we have shown that portal, GLP-1-dependent, glucose sensing is impaired and a low-dose dihydrotestosterone (DHT) implant inserted into the area of the portal sensor normalizes glucose metabolism acutely. We evaluated the capacity of portal DHT to achieve sustained remission of diabetes and its impact on cardiovascular and renal function.Methods: Three groups of six minipigs (aged 3yr) were used. In two groups, diabetes was induced (obesogenic diet plus streptozotocin 80 mg/kg, IV). In half of these, a silicon implant delivering 100μg/24H DHT was inserted laparoscopically in the region of the GLP-1r (DHT); the other half received a sham implant (Sham). The third group was fed a non-obesogenic diet (Lean). One year following implant insertion, daily glucose (CGM), fasting plasma insulin, insulin sensitivity (euglycemic hyperinsulinemic clamp), cardiovascular function (HF oscillometry, Doppler ultrasound, and gated 18 FDG PET) and glomerular filtration rate (68 Ga DOTA PET), were measured.Results: Data are presented in the table. Conclusion: In a large animal model of T2D, low-dose, portal DHT administration has sustained effects to improve both glycemic control and insulin sensitivity, and preserves cardiovascular and renal function.
C. Malbert: None. M.R. Allouche: None. M. Horowitz: None. K.L. Jones: None.
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